187 results on '"De Wever, O."'
Search Results
2. Benchmarking blood collection tubes and processing intervals for extracellular vesicle performance metrics
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Dhondt, B. (Bert), Pinheiro, C. (Cláudio), Geeurickx, E. (Edward), Tulkens, J. (Joeri), Vergauwen, G. (Glenn), Van Der Pol, E. (Edwin), Nieuwland, R. (Rienk), Decock, A. (Anneleen), Miinalainen, I. (Ilkka), Rappu, P. (Pekka), Schroth, G. (Gary), Kuersten, S. (Scott), Vandesompele, J. (Jo), Mestdagh, P. (Pieter), Lumen, N. (Nicolaas), De Wever, O. (Olivier), Hendrix, A. (An), Dhondt, B. (Bert), Pinheiro, C. (Cláudio), Geeurickx, E. (Edward), Tulkens, J. (Joeri), Vergauwen, G. (Glenn), Van Der Pol, E. (Edwin), Nieuwland, R. (Rienk), Decock, A. (Anneleen), Miinalainen, I. (Ilkka), Rappu, P. (Pekka), Schroth, G. (Gary), Kuersten, S. (Scott), Vandesompele, J. (Jo), Mestdagh, P. (Pieter), Lumen, N. (Nicolaas), De Wever, O. (Olivier), and Hendrix, A. (An) more...
- Abstract
The analysis of extracellular vesicles (EV) in blood samples is under intense investigation and holds the potential to deliver clinically meaningful biomarkers for health and disease. Technical variation must be minimized to confidently assess EV-associated biomarkers, but the impact of pre-analytics on EV characteristics in blood samples remains minimally explored. We present the results from the first large-scale EV Blood Benchmarking (EVBB) study in which we systematically compared 11 blood collection tubes (BCT; six preservation and five non-preservation) and three blood processing intervals (BPI; 1, 8 and 72 h) on defined performance metrics (n = 9). The EVBB study identifies a significant impact of multiple BCT and BPI on a diverse set of metrics reflecting blood sample quality, ex-vivo generation of blood-cell derived EV, EV recovery and EV-associated molecular signatures. The results assist the informed selection of the optimal BCT and BPI for EV analysis. The proposed metrics serve as a framework to guide future research on pre-analytics and further support methodological standardization of EV studies. more...
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- 2023
Catalog
3. Depletion of soluble cytokines unlocks the immunomodulatory bioactivity of extracellular vesicles
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Roux, Q. (Quentin), Boiy, R. (Robin), De Vuyst, F. (Felix), Tkach, M. (Mercedes), Pinheiro, C. (Claudio), de Geyter, S. (Sofie), Miinalainen, I. (Ilkka), Théry, C. (Clotilde), De Wever, O. (Olivier), Hendrix, A. (An), Roux, Q. (Quentin), Boiy, R. (Robin), De Vuyst, F. (Felix), Tkach, M. (Mercedes), Pinheiro, C. (Claudio), de Geyter, S. (Sofie), Miinalainen, I. (Ilkka), Théry, C. (Clotilde), De Wever, O. (Olivier), and Hendrix, A. (An) more...
- Abstract
Despite an enormous interest in understanding the bioactivity of extracellular vesicles (EV) in physiology and disease for the development of therapeutic applications, the impact of EV preparation methods remains minimally explored. In this study, we implemented density gradient ultracentrifugation combined with size-exclusion chromatography (DG-SEC), differential ultracentrifugation (dUC) and/or stand-alone SEC (sSEC) to fractionate media conditioned by different cancer cells and/or cancer-associated fibroblasts (CAF). EV-enriched but protein-depleted versus EV-depleted but protein-enriched DG-SEC fractions, and EV-containing dUC and sSEC preparations were quality controlled for particle number, protein concentration, selected protein composition and ultrastructure, characterized for their cytokine content, and dose-dependently evaluated for monocyte-derived dendritic cell (MoDC) maturation by measuring surface marker expression and/or cytokine secretion. EV preparations obtained by DG-SEC from media conditioned by different cancer cell lines or CAF, were depleted from soluble immune suppressive cytokines such as VEGF-A and MCP-1 and potently stimulated MoDC maturation. In contrast, EV-containing dUC or sSEC preparations were not depleted from these soluble cytokines and were unable to mature MoDC. Subsequent processing of dUC EV preparations by SEC dose-dependently restored the immunomodulatory bioactivity. Overall, our results demonstrate that method-dependent off-target enrichment of soluble cytokines has implications for the study of EV immunomodulatory bioactivity and warrants careful consideration. more...
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- 2023
4. Integrating automated liquid handling in the separation workflow of extracellular vesicles enhances specificity and reproducibility
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Van Dorpe, S. (Sofie), Lippens, L. (Lien), Boiy, R. (Robin), Pinheiro, C. (Cláudio), Vergauwen, G. (Glenn), Rappu, P. (Pekka), Miinalainen, I. (Ilkka), Tummers, P. (Philippe), Denys, H. (Hannelore), De Wever, O. (Olivier), Hendrix, A. (An), Van Dorpe, S. (Sofie), Lippens, L. (Lien), Boiy, R. (Robin), Pinheiro, C. (Cláudio), Vergauwen, G. (Glenn), Rappu, P. (Pekka), Miinalainen, I. (Ilkka), Tummers, P. (Philippe), Denys, H. (Hannelore), De Wever, O. (Olivier), and Hendrix, A. (An) more...
- Abstract
Background: Extracellular vesicles (EV) are extensively studied in human body fluids as potential biomarkers for numerous diseases. Major impediments of EV-based biomarker discovery include the specificity and reproducibility of EV sample preparation as well as intensive manual labor. We present an automated liquid handling workstation for the density-based separation of EV from human body fluids and compare its performance to manual handling by (in)experienced researchers. Results: Automated versus manual density-based separation of trackable recombinant extracellular vesicles (rEV) spiked in PBS significantly reduces variability in rEV recovery as quantified by fluorescent nanoparticle tracking analysis and ELISA. To validate automated density-based EV separation from complex body fluids, including blood plasma and urine, we assess reproducibility, recovery, and specificity by mass spectrometry-based proteomics and transmission electron microscopy. Method reproducibility is the highest in the automated procedure independent of the matrix used. While retaining (in urine) or enhancing (in plasma) EV recovery compared to manual liquid handling, automation significantly reduces the presence of body fluid specific abundant proteins in EV preparations, including apolipoproteins in plasma and Tamm-Horsfall protein in urine. Conclusions: In conclusion, automated liquid handling ensures cost-effective EV separation from human body fluids with high reproducibility, specificity, and reduced hands-on time with the potential to enable larger-scale biomarker studies. more...
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- 2023
5. JAK3 deregulation by activating mutations confers invasive growth advantage in extranodal nasal-type natural killer cell lymphoma
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Bouchekioua, A, Scourzic, L, de Wever, O, Zhang, Y, Cervera, P, Aline-Fardin, A, Mercher, T, Gaulard, P, Nyga, R, Jeziorowska, D, Douay, L, Vainchenker, W, Louache, F, Gespach, C, Solary, E, and Coppo, P more...
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- 2014
- Full Text
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6. Performance evaluation of RNA purification kits and blood collection tubes in the Extracellular RNA Quality Control (exRNAQC) study
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Bert Dhondt, Gary P. Schroth, Celine Everaert, Avila Cobos F, Jasper Anckaert, Nurten Yigit, Jill Deleu, Eva Hulstaert, Van Maerken T, Vanden Eynde E, Piofczyk T, Scott Kuersten, Annelien Morlion, De Wever O, Anneleen Decock, De Wilde J, Kathleen Schoofs, Pieter Mestdagh, Kimberly Verniers, Thibaut D’huyvetter, An Hendrix, Justine Nuytens, Philippron A, Hetty Helsmoortel, Jo Vandesompele, Van Paemel R, Nele Nijs, and Carolina Fierro more...
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Transcriptome ,Messenger RNA ,RNA ,RNA extraction ,Computational biology ,Sample collection ,Biology ,Blood Collection Tube ,Gene ,Extracellular RNA - Abstract
The use of blood-based extracellular RNA (cell-free RNA; exRNA) as clinical biomarker requires the implementation of a validated procedure for sample collection, processing, and profiling. So far, no study has systematically addressed the pre-analytical variables affecting transcriptome analysis of exRNAs. In the exRNAQC study, we evaluated ten blood collection tubes, three time intervals between blood draw and downstream processing, and eight RNA purification methods using the supplier-specified minimum and maximum biofluid input volumes. The impact of these pre-analytics on deep transcriptome profiling of both small and messenger RNA from healthy donors’ plasma or serum was assessed for each pre-analytical variable separately and for interactions between a selected set of pre-analytics, resulting in 456 extracellular transcriptomes. Making use of 189 synthetic spike-in RNAs, the processing and analysis workflow was controlled. When comparing blood collection tubes, so-called preservation tubes do not stabilize exRNA well, and result in variable RNA concentration and sensitivity (i.e., the number of detected RNAs) over time, as well as compromised reproducibility. We also document large differences in RNA purification kit performance in terms of sensitivity, reproducibility, and observed transcriptome complexity, and demonstrate interactions between specific blood collection tubes, purification kits and time intervals. Our results are summarized in 11 performance metrics that enable an informed selection of the most optimal sample processing workflow for a given experiment. In conclusion, we put forward robust quality control metrics for exRNA quantification methods with validated standard operating procedures (SOPs), representing paramount groundwork for future exRNA-based precision medicine applications. more...
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- 2021
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7. Robust sequential biophysical fractionation of blood plasma to study variations in the biomolecular landscape of systemically circulating extracellular vesicles across clinical conditions
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Vergauwen, G. (Glenn), Tulkens, J. (Joeri), Pinheiro, C. (Cláudio), Cobos, F. A. (Francisco Avila), Dedeyne, S. (Sándor), De Scheerder, M.-A. (Marie-Angélique), Vandekerckhove, L. (Linos), Impens, F. (Francis), Miinalainen, I. (Ilkka), Gevaert, K. (Kris), Mestdagh, P. (Pieter), Vandesompele, J. (Jo), Denys, H. (Hannelore), De Wever, O. (Olivier), and Hendrix, A. (An) more...
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separation ,transcriptomics ,proteomics ,blood ,biomarkers ,exosomes ,extracellular vesicles ,corona ,isolation ,lipoprotein particles - Abstract
Separating extracellular vesicles (EV) from blood plasma is challenging and complicates their biological understanding and biomarker development. In this study, we fractionate blood plasma by combining size-exclusion chromatography (SEC) and OptiPrep density gradient centrifugation to study clinical context-dependent and time-dependent variations in the biomolecular landscape of systemically circulating EV. Using pooled blood plasma samples from breast cancer patients, we first demonstrate the technical repeatability of blood plasma fractionation. Using serial blood plasma samples from HIV and ovarian cancer patients (n = 10) we next show that EV carry a clinical context-dependent and/or time-dependent protein and small RNA composition, including miRNA and tRNA. In addition, differential analysis of blood plasma fractions provides a catalogue of putative proteins not associated with systemically circulating EV. In conclusion, the implementation of blood plasma fractionation allows to advance the biological understanding and biomarker development of systemically circulating EV. more...
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- 2021
8. Autocrine induction of invasion and metastasis by tumor-associated trypsin inhibitor in human colon cancer cells
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Gouyer, V, Fontaine, D, Dumont, P, de Wever, O, Fontayne-Devaud, H, Leteurtre, E, Truant, S, Delacour, D, Drobecq, H, Kerckaert, J-P, de Launoit, Y, Bracke, M, Gespach, C, Desseyn, J-L, and Huet, G
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- 2008
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9. Opposing roles of netrin-1 and the dependence receptor DCC in cancer cell invasion, tumor growth and metastasis
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Rodrigues, S, De Wever, O, Bruyneel, E, Rooney, R J, and Gespach, C
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- 2007
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10. Increased levels of systemic LPS-positive bacterial extracellular vesicles in patients with intestinal barrier dysfunction
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Tulkens, J. (Joeri), Vergauwen, G. (Glenn), Van Deun, J. (Jan), Geeurickx, E. (Edward), Dhondt, B. (Bert), Lippens, L. (Lien), De Scheerder, A. (Angélique), Miinalainen, I. (Ilkka), Rappu, P. (Pekka), De Geest, B. G. (Bruno G.), Vandecasteele, K. (Katrien), Laukens, D. (Debby), Vandekerckhove, L. (Linos), Denys, H. (Hannelore), Vandesompele, J. (Jo), De Wever, O. (Olivier), Hendrix, A. (An), Tulkens, J. (Joeri), Vergauwen, G. (Glenn), Van Deun, J. (Jan), Geeurickx, E. (Edward), Dhondt, B. (Bert), Lippens, L. (Lien), De Scheerder, A. (Angélique), Miinalainen, I. (Ilkka), Rappu, P. (Pekka), De Geest, B. G. (Bruno G.), Vandecasteele, K. (Katrien), Laukens, D. (Debby), Vandekerckhove, L. (Linos), Denys, H. (Hannelore), Vandesompele, J. (Jo), De Wever, O. (Olivier), and Hendrix, A. (An) more...
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- 2020
11. Feasibility of mechanical extrusion to coat nanoparticles with extracellular vesicle membranes
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Van Deun, J. (Jan), Roux, Q. (Quentin), Deville, S. (Sarah), Van Acker, T. (Thibaut), Rappu, P. (Pekka), Miinalainen, I. (Ilkka), Heino, J. (Jyrki), Vanhaecke, F. (Frank), De Geest, B. G. (Bruno G.), De Wever, O. (Olivier), Hendrix, A. (An), Van Deun, J. (Jan), Roux, Q. (Quentin), Deville, S. (Sarah), Van Acker, T. (Thibaut), Rappu, P. (Pekka), Miinalainen, I. (Ilkka), Heino, J. (Jyrki), Vanhaecke, F. (Frank), De Geest, B. G. (Bruno G.), De Wever, O. (Olivier), and Hendrix, A. (An) more...
- Abstract
Biomimetic functionalization to confer stealth and targeting properties to nanoparticles is a field of intense study. Extracellular vesicles (EV), sub-micron delivery vehicles for intercellular communication, have unique characteristics for drug delivery. We investigated the top-down functionalization of gold nanoparticles with extracellular vesicle membranes, including both lipids and associated membrane proteins, through mechanical extrusion. EV surface-exposed membrane proteins were confirmed to help avoid unwanted elimination by macrophages, while improving autologous uptake. EV membrane morphology, protein composition and orientation were found to be unaffected by mechanical extrusion. We implemented complementary EV characterization methods, including transmission- and immune-electron microscopy, and nanoparticle tracking analysis, to verify membrane coating, size and zeta potential of the EV membrane-cloaked nanoparticles. While successful EV membrane coating of the gold nanoparticles resulted in lower macrophage uptake, low yield was found to be a significant downside of the extrusion approach. Our data incentivize more research to leverage EV membrane biomimicking as a unique drug delivery approach in the near future. more...
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- 2020
12. Unravelling the proteomic landscape of extracellular vesicles in prostate cancer by density-based fractionation of urine
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Dhondt, B. (Bert), Geeurickx, E. (Edward), Tulkens, J. (Joeri), Van Deun, J. (Jan), Vergauwen, G. (Glenn), Lippens, L. (Lien), Miinalainen, I. (Ilkka), Rappu, P. (Pekka), Heino, J. (Jyrki), Ost, P. (Piet), Lumen, N. (Nicolaas), De Wever, O. (Olivier), Hendrix, A. (An), Dhondt, B. (Bert), Geeurickx, E. (Edward), Tulkens, J. (Joeri), Van Deun, J. (Jan), Vergauwen, G. (Glenn), Lippens, L. (Lien), Miinalainen, I. (Ilkka), Rappu, P. (Pekka), Heino, J. (Jyrki), Ost, P. (Piet), Lumen, N. (Nicolaas), De Wever, O. (Olivier), and Hendrix, A. (An) more...
- Abstract
Extracellular vesicles (EV) are increasingly being recognized as important vehicles of intercellular communication and promising diagnostic and prognostic biomarkers in cancer. Despite this enormous clinical potential, the plethora of methods to separate EV from biofluids, providing material of highly variable purity, and lacking knowledge regarding methodological repeatability pose a barrier to clinical translation. Urine is considered an ideal proximal fluid for the study of EV in urological cancers due to its direct contact with the urogenital system. We demonstrate that density-based fractionation of urine by bottom-up Optiprep density gradient centrifugation separates EV and soluble proteins with high specificity and repeatability. Mass spectrometry-based proteomic analysis of urinary EV (uEV) in men with benign and malignant prostate disease allowed us to significantly expand the known human uEV proteome with high specificity and identifies a unique biological profile in prostate cancer not uncovered by the analysis of soluble proteins. In addition, profiling the proteome of EV separated from prostate tumour conditioned medium and matched uEV confirms the specificity of the identified uEV proteome for prostate cancer. Finally, a comparative proteomic analysis with uEV from patients with bladder and renal cancer provided additional evidence of the selective enrichment of protein signatures in uEV reflecting their respective cancer tissues of origin. In conclusion, this study identifies hundreds of previously undetected proteins in uEV of prostate cancer patients and provides a powerful toolbox to map uEV content and contaminants ultimately allowing biomarker discovery in urological cancers. more...
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- 2020
13. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines
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Théry, C, Witwer, KW, Aikawa, E, Alcaraz, MJ, Anderson, JD, Andriantsitohaina, R, Antoniou, A, Arab, T, Archer, F, Atkin-Smith, GK, Ayre, DC, Bach, JM, Bachurski, D, Baharvand, H, Balaj, L, Baldacchino, S, Bauer, NN, Baxter, AA, Bebawy, M, Beckham, C, Bedina Zavec, A, Benmoussa, A, Berardi, AC, Bergese, P, Bielska, E, Blenkiron, C, Bobis-Wozowicz, S, Boilard, E, Boireau, W, Bongiovanni, A, Borràs, FE, Bosch, S, Boulanger, CM, Breakefield, X, Breglio, AM, Brennan, M, Brigstock, DR, Brisson, A, Broekman, MLD, Bromberg, JF, Bryl-Górecka, P, Buch, S, Buck, AH, Burger, D, Busatto, S, Buschmann, D, Bussolati, B, Buzás, EI, Byrd, JB, Camussi, G, Carter, DRF, Caruso, S, Chamley, LW, Chang, YT, Chaudhuri, AD, Chen, C, Chen, S, Cheng, L, Chin, AR, Clayton, A, Clerici, SP, Cocks, A, Cocucci, E, Coffey, RJ, Cordeiro-da-Silva, A, Couch, Y, Coumans, FAW, Coyle, B, Crescitelli, R, Criado, MF, D’Souza-Schorey, C, Das, S, de Candia, P, De Santana, EF, De Wever, O, del Portillo, HA, Demaret, T, Deville, S, Devitt, A, Dhondt, B, Di Vizio, D, Dieterich, LC, Dolo, V, Dominguez Rubio, AP, Dominici, M, Dourado, MR, Driedonks, TAP, Duarte, FV, Duncan, HM, Eichenberger, RM, Ekström, K, EL Andaloussi, S, Elie-Caille, C, Erdbrügger, U, Falcón-Pérez, JM, Fatima, F, Fish, JE, Flores-Bellver, M, Försönits, A, Frelet-Barrand, A, and HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. more...
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ectosomes ,microparticles ,standardization ,minimal information requirements ,exosomes ,guidelines ,Biochemistry and Cell Biology ,extracellular vesicles ,microvesicles ,reproducibility ,rigor - Abstract
© 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points. more...
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- 2019
14. Splenic metabolic activity as biomarker in cervical cancer
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De Jaeghere, E.A., primary, Laloo, F., additional, Lippens, L., additional, De Man, K., additional, Van Bockstal, M., additional, Van de Vijver, K., additional, Tummers, P., additional, Makar, A., additional, De Visschere, P., additional, De Wever, O., additional, Amant, F., additional, Denys, H., additional, and Vandecasteele, K., additional more...
- Published
- 2019
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15. Stromal integrin alpha 11 regulates PDGFRβ signaling and promotes breast cancer progression
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Primac, I. (Irina), Maquoi, E. (Erik), Blacher, S. (Silvia), Heljasvaara, R. (Ritva), Van Deun, J. (Jan), Smeland, H. Y. (Hilde Y.H.), Canale, A. (Annalisa), Louis, T. (Thomas), Stuhr, L. (Linda), Sounni, N. E. (Nor Eddine), Cataldo, D. (Didier), Pihlajaniemi, T. (Taina), Pequeux, C. (Christel), De Wever, O. (Olivier), Gullberg, D. (Donald), Noel, A. (Agnès), Primac, I. (Irina), Maquoi, E. (Erik), Blacher, S. (Silvia), Heljasvaara, R. (Ritva), Van Deun, J. (Jan), Smeland, H. Y. (Hilde Y.H.), Canale, A. (Annalisa), Louis, T. (Thomas), Stuhr, L. (Linda), Sounni, N. E. (Nor Eddine), Cataldo, D. (Didier), Pihlajaniemi, T. (Taina), Pequeux, C. (Christel), De Wever, O. (Olivier), Gullberg, D. (Donald), and Noel, A. (Agnès) more...
- Abstract
Cancer-associated fibroblasts (CAFs) are key actors in modulating the progression of many solid tumors, such as breast cancer (BC). Herein, we identify an integrin α11/PDGFRβ–positive CAF subset displaying tumor-promoting features in BC. In the preclinical MMTV-PyMT mouse model, integrin α11 deficiency led to a drastic reduction of tumor progression and metastasis. A clear association between integrin α11 and PDGFRβ was found at both transcriptional and histological levels in BC specimens. High stromal integrin α11/PDGFRβ expression was associated with high grades and poorer clinical outcome in human BC patients. Functional assays using 5 CAF subpopulations (1 murine, 4 human) revealed that integrin α11 promotes CAF invasion and CAF-induced tumor cell invasion upon PDGF-BB stimulation. Mechanistically, the proinvasive activity of integrin α11 relies on its ability to interact with PDGFRβ in a ligand-dependent manner and to promote its downstream JNK activation, leading to the production of tenascin C, a proinvasive matricellular protein. Pharmacological inhibition of PDGFRβ and JNK impaired tumor cell invasion induced by integrin α11+ CAFs. Collectively, our study uncovers an integrin α11+ subset of protumoral CAFs that exploits the PDGFRβ/JNK signaling axis to promote tumor invasiveness in BC. more...
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- 2019
16. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines
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Thery, C., Witwer, K. (Kenneth), Aikawa, E. (Elena), Alcaraz, M.J. (Maria Jose), Anderson, J.D. (Johnathon D), Andriantsitohaina, R. (Ramaroson), Antoniou, A. (Anna), Arab, T. (Tanina), Archer, F. (Fabienne), Atkin-Smith, G.K. (Georgia K), Ayre, D.C. (D Craig), Bach, J.-M. (Jean-Marie), Bachurski, D. (Daniel), Baharvand, H. (Hossein), Balaj, L. (Leonora), Baldacchino, S. (Shawn), Bauer, N.N. (Natalie N), Baxter, A.A. (Amy A), Bebawy, M. (Mary), Beckham, C. (Carla), Bedina Zavec, A. (Apolonija), Benmoussa, A. (Abderrahim), Berardi, A.C. (Anna C), Bergese, P. (Paolo), Bielska, E. (Ewa), Blenkiron, C. (Cherie), Bobis-Wozowicz, S. (Sylwia), Boilard, E. (Eric), Boireau, W. (Wilfrid), Bongiovanni, A. (Antonella), Borràs, F.E. (Francesc), Bosch, S. (Steffi), Boulanger, C.M. (Chantal), Breakefield, X. (Xandra), Breglio, A.M. (Andrew M), Brennan, M.Á. (Meadhbh Á), Brigstock, D.R. (David R), Brisson, A. (Alain), Broekman, M.L.D. (Marike), Bromberg, J.F. (Jacqueline F), Bryl-Górecka, P. (Paulina), Buch, S. (Shilpa), Buck, A.H. (Amy H), Burger, D. (Dylan), Busatto, S. (Sara), Buschmann, D. (Dominik), Bussolati, B. (Benedetta), Buzas, E. (Edit), Byrd, J.B. (James Bryan), Camussi, G. (Giovanni), Carter, D.R.F. (David RF), Caruso, S. (Sarah), Chamley, L.W. (Lawrence W), Chang, Y.-T. (Yu-Ting), Chaudhuri, A.D. (Amrita Datta), Chen, C. (Chihchen), Chen, S. (Shuai), Cheng, L. (Lesley), Chin, A.R. (Andrew R), Clayton, A. (Aled), Clerici, S.P. (Stefano P), Cocks, A. (Alex), Cocucci, E. (Emanuele), Coffey, R.J. (Robert J), Cordeiro-da-Silva, A. (Anabela), Couch, Y. (Yvonne), Coumans, F.A.W. (Frank AW), Coyle, B. (Beth), Crescitelli, R. (Rossella), Criado, M.F. (Miria Ferreira), D’Souza-Schorey, C. (Crislyn), Das, S. (Saumya), de Candia, P. (Paola), De Santana, E.F. (Eliezer F), De Wever, O. (Olivier), Del Portillo, H. (Hernando), Demaret, T. (Tanguy), Deville, S. (Sarah), Devitt, A. (Andrew), Dhondt, B. (Bert), Di Vizio, D. (Dolores), Dieterich, L.C. (Lothar C), Dolo, V. (Vincenza), Dominguez Rubio, A.P. (Ana Paula), Dominici, M. (Massimo), Dourado, M.R. (Mauricio R), Driedonks, T.A.P. (Tom AP), Duarte, F.V. (Filipe V), Duncan, H.M. (Heather M), Eichenberger, R.M. (Ramon M), Ekström, K. (Karin), EL Andaloussi, S. (Samir), Elie-Caille, C. (Celine), Erdbrügger, U. (Uta), Falcon-Perez, J.M. (Juan), Fatima, F. (Farah), Fish, J.E. (Jason E), Flores-Bellver, M. (Miguel), Försönits, A. (András), Frelet-Barrand, A. (Annie), Fricke, F. (Fabia), Fuhrmann, G. (Gregor), Gabrielsson, S. (Susanne), Gámez-Valero, A. (Ana), Gardiner, C. (Chris), Gärtner, K. (Kathrin), Gaudin, R. (Raphael), Gho, Y.S. (Yong Song), Giebel, B. (B.), Gilbert, C. (Caroline), Gimona, M. (Mario), Giusti, I. (Ilaria), Goberdhan, D.C.I. (Deborah CI), Görgens, A. (André), Gorski, S.M. (Sharon M), Greening, D.W. (David W.), Gross, J.C. (Julia Christina), Gualerzi, A. (Alice), Gupta, G.N. (Gopal N), Gustafson, D. (Dakota), Handberg, A. (Aase), Haraszti, R.A. (Reka A), Harrison, P. (Paul), Hegyesi, H. (Hargita), Hendrix, A. (An), Hill, A.F. (Andrew F), Hochberg, F.H. (Fred H), Hoffmann, K.F. (Karl F), Holder, B. (Beth), Holthofer, H. (Harry), Hosseinkhani, B. (Baharak), Hu, G. (Guoku), Huang, Y. (Yiyao), Huber, V. (Veronica), Hunt, S. (Stuart), Ibrahim, A.G.-E. (Ahmed Gamal-Eldin), Ikezu, T. (Tsuneya), Inal, J.M. (Jameel), Isin, M. (Mustafa), Ivanova, A. (Alena), Jackson, H.K. (Hannah K), Jacobsen, S. (Soren), Jay, S.M. (Steven M), Jayachandran, M. (Muthuvel), Jenster, G.W. (Guido), Jiang, L. (Lanzhou), Johnson, S.M. (Suzanne M), Jones, J.C. (Jennifer C), Jong, A. (Ambrose), Jovanovic-Talisman, T. (Tijana), Jung, S. (Stephanie), Kalluri, R. (Raghu), Kano, S.-I. (Shin-ichi), Kaur, S. (Sukhbir), Kawamura, Y. (Yumi), Keller, E.T. (Evan T), Khamari, D. (Delaram), Khomyakova, E. (Elena), Khvorova, A. (Anastasia), Kierulf, P. (Peter), Kim, K.P. (Kwang Pyo), Kislinger, T. (Thomas), Klingeborn, M. (Mikael), Klinke, D.J. (David J), Kornek, M. (Miroslaw), Kosanović, M.M. (Maja M), Kovács, Á.F. (Árpád Ferenc), Krämer-Albers, E.-M. (Eva-Maria), Krasemann, S. (Susanne), Krause, M. (Mirja), Kurochkin, I.V. (Igor V), Kusuma, G.D. (Gina D), Kuypers, S. (Sören), Laitinen, S. (Saara), Langevin, S.M. (Scott M), Languino, L.R. (Lucia R), Lannigan, J. (Joanne), Lässer, C. (Cecilia), Laurent, L.C. (Louise C), Lavieu, G. (Gregory), Lázaro-Ibáñez, E. (Elisa), Le Lay, S. (Soazig), Lee, M.-S. (Myung-Shin), Lee, Y.X.F. (Yi Xin Fiona), Lemos, D.S. (Debora S), Lenassi, M. (Metka), Leszczynska, A. (Aleksandra), Li, I.T.S. (Isaac TS), Liao, K. (Ke), Libregts, S.F. (Sten), Ligeti, E. (Erzsebet), Lim, R. (Rebecca), Lim, S.K. (Sai Kiang), Linē, A. (Aija), Linnemannstöns, K. (Karen), Llorente, A. (Alicia), Lombard, C.A. (Catherine A), Lorenowicz, M.J. (Magdalena J), Lörincz, Á.M. (Ákos M), Lötvall, J. (Jan), Lovett, J. (Jason), Lowry, M.C. (Michelle C), Loyer, X. (Xavier), Lu, Q. (Quan), Lukomska, B. (Barbara), Lunavat, T.R. (Taral R), Maas, S.L.N. (Sybren), Malhi, H. (Harmeet), Marcilla, A. (Antonio), Mariani, J. (Jacopo), Mariscal, J. (Javier), Martens-Uzunova, E.S. (Elena), Martin-Jaular, L. (Lorena), Martinez, M.C. (M Carmen), Martins, V.R. (Vilma Regina), Mathieu, M. (Mathilde), Mathivanan, S. (Suresh), Maugeri, M. (Marco), McGinnis, L.K. (Lynda K), McVey, M.J. (Mark J), Meckes, D.G. (David G), Meehan, K.L. (Katie L), Mertens, I. (Inge), Minciacchi, V.R. (Valentina R), Möller, A. (Andreas), Møller Jørgensen, M. (Malene), Morales-Kastresana, A. (Aizea), Morhayim, J. (Jess), Mullier, F. (Francois), Muraca, M. (Maurizio), Musante, L. (Luca), Mussack, V. (Veronika), Muth, D.C. (Dillon C), Myburgh, K.H. (Kathryn H), Najrana, T. (Tanbir), Nawaz, M. (Muhammad), Nazarenko, I. (Irina), Nejsum, P. (Peter), Neri, C. (Christian), Neri, T. (Tommaso), Nieuwland, C.C.M. (Carolien) van, Nimrichter, L. (Leonardo), Nolan, J.P. (John P), Nolte-’t Hoen, E.N.M. (Esther NM), Hooten, N.N. (Nicole Noren), O’Driscoll, L. (Lorraine), O’Grady, T. (Tina), O’Loghlen, A. (Ana), Ochiya, T. (Takahiro), Olivier, M. (Martin), Ortiz, A. (Alberto), Ortiz, L.A. (Luis A), Osteikoetxea, X. (Xabier), Ostegaard, O. (Ole), Ostrowski, M. (Matias), Park, J. (Jaesung), Pegtel, D.M. (D. Michiel), Peinado, H. (Hector), Perut, F. (Francesca), Pfaffl, M.W. (Michael W), Phinney, D.G. (Donald G), Pieters, B.C.H. (Bartijn CH), Pink, R.C. (Ryan C), Pisetsky, D.S. (David S), Pogge von Strandmann, E. (Elke), Polakovicova, I. (Iva), Poon, I.K.H. (Ivan KH), Powell, B.H. (Bonita H), Prada, I. (Ilaria), Pulliam, L. (Lynn), Quesenberry, P. (Peter), Radeghieri, A. (Annalisa), Raffai, R.L. (Robert L), Raimondo, S. (Stefania), Rak, J. (Janusz), Ramirez, M.I. (Marcel I.), Raposo, L. (Luís), Rayyan, M.S. (Morsi S), Regev-Rudzki, N. (Neta), Ricklefs, F.L. (Franz L), Robbins, P.D. (Paul D), Roberts, D.D. (David D), Rodrigues, S.C. (Silvia C), Rohde, E. (Eva), Rome, S. (Sophie), Rouschop, K.M.A. (Kasper MA), Rughetti, A. (Aurelia), Russell, A.E. (Ashley E), Saá, P. (Paula), Sahoo, S. (Susmita), Salas-Huenuleo, E. (Edison), Sánchez, C. (Catherine), Saugstad, J.A. (Julie A), Saul, M.J. (Meike J), Schiffelers, R.M. (Raymond), Schneider, R. (Raphael), Schøyen, T.H. (Tine Hiorth), Scott, A. (Aaron), Shahaj, E. (Eriomina), Sharma, S. (Shivani), Shatnyeva, O. (Olga), Shekari, F. (Faezeh), Shelke, G.V. (Ganesh Vilas), Shetty, A.K. (Ashok K), Shiba, K. (Kiyotaka), Siljander, P. (Pia), Silva, A.M. (Andreia M), Skowronek, A. (Agata), Snyder, O.L. (Orman L), Soares, R.P. (Rodrigo Pedro), Sódar, B.W. (Barbara W), Soekmadji, C. (Carolina), Sotillo, J. (Javier), Stahl, P.D. (Philip D), Stoorvogel, W. (Willem), Stott, S.L. (Shannon L), Strasser, E.F. (Erwin F), Swift, S. (Simon), Tahara, H. (Hidetoshi), Tewari, M. (Muneesh), Timms, K. (Kate), Tiwari, S. (Swasti), Tixeira, R. (Rochelle), Tkach, M. (Mercedes), Toh, W.S. (Wei Seong), Tomasini, R. (Richard), Torrecilhas, A.C. (Ana Claudia), Tosar, J.P. (Juan Pablo), Toxavidis, V. (Vasilis), Urbanelli, L. (Lorena), Vader, P. (Pieter), Balkom, B.W.M. (Bas) van, van der Grein, S.G. (Susanne G), Van Deun, J. (Jan), van Herwijnen, M.J.C. (Martijn JC), Van Keuren-Jensen, K. (Kendall), van Niel, G. (Guillaume), Royen, M.E. (Martin), van Wijnen, A.J. (Andre J), Vasconcelos, M.H. (M Helena), Vechetti, I.J. (Ivan J), Veit, T.D. (Tiago D), Vella, L.J. (Laura J.), Velot, É. (Émilie), Verweij, F.J. (Frederik J), Vestad, B. (Beate), Viñas, J.L. (Jose L), Visnovitz, T. (Tamás), Vukman, K.V. (Krisztina V), Wahlgren, J. (Jessica), Watson, D.C. (Dionysios C), Wauben, M.H.M. (Marca), Weaver, A. (Alissa), Webber, J.P. (Jason P), Weber, V. (Viktoria), Wehman, A.M. (Ann M), Weiss, D.J. (Daniel J), Welsh, J.A. (Joshua A), Wendt, S. (Sebastian), Wheelock, A.M. (Asa M), Wiener, Z. (Zoltán), Witte, L. (Leonie), Wolfram, J. (Joy), Xagorari, A. (Angeliki), Xander, P. (Patricia), Xu, J. (Jing), Yan, X. (Xiaomei), Yáñez-Mó, M. (María), Yin, H. (Hang), Yuana, Y., Zappulli, V. (Valentina), Zarubova, J. (Jana), Žėkas, V. (Vytautas), Zhang, J.-Y. (Jian-ye), Zhao, Z. (Zezhou), Zheng, L. (Lei), Zheutlin, A.R. (Alexander R), Zickler, A.M. (Antje M), Zimmermann, P. (Pascale), Zivkovic, A.M. (Angela M), Zocco, D. (Davide), Zuba-Surma, E.K. (Ewa K), Thery, C., Witwer, K. (Kenneth), Aikawa, E. (Elena), Alcaraz, M.J. (Maria Jose), Anderson, J.D. (Johnathon D), Andriantsitohaina, R. (Ramaroson), Antoniou, A. (Anna), Arab, T. (Tanina), Archer, F. (Fabienne), Atkin-Smith, G.K. (Georgia K), Ayre, D.C. (D Craig), Bach, J.-M. (Jean-Marie), Bachurski, D. (Daniel), Baharvand, H. (Hossein), Balaj, L. (Leonora), Baldacchino, S. (Shawn), Bauer, N.N. (Natalie N), Baxter, A.A. (Amy A), Bebawy, M. (Mary), Beckham, C. (Carla), Bedina Zavec, A. (Apolonija), Benmoussa, A. (Abderrahim), Berardi, A.C. (Anna C), Bergese, P. (Paolo), Bielska, E. (Ewa), Blenkiron, C. (Cherie), Bobis-Wozowicz, S. (Sylwia), Boilard, E. (Eric), Boireau, W. (Wilfrid), Bongiovanni, A. (Antonella), Borràs, F.E. (Francesc), Bosch, S. (Steffi), Boulanger, C.M. (Chantal), Breakefield, X. (Xandra), Breglio, A.M. (Andrew M), Brennan, M.Á. (Meadhbh Á), Brigstock, D.R. (David R), Brisson, A. (Alain), Broekman, M.L.D. (Marike), Bromberg, J.F. (Jacqueline F), Bryl-Górecka, P. (Paulina), Buch, S. (Shilpa), Buck, A.H. (Amy H), Burger, D. (Dylan), Busatto, S. (Sara), Buschmann, D. (Dominik), Bussolati, B. (Benedetta), Buzas, E. (Edit), Byrd, J.B. (James Bryan), Camussi, G. (Giovanni), Carter, D.R.F. (David RF), Caruso, S. (Sarah), Chamley, L.W. (Lawrence W), Chang, Y.-T. (Yu-Ting), Chaudhuri, A.D. (Amrita Datta), Chen, C. (Chihchen), Chen, S. (Shuai), Cheng, L. (Lesley), Chin, A.R. (Andrew R), Clayton, A. (Aled), Clerici, S.P. (Stefano P), Cocks, A. (Alex), Cocucci, E. (Emanuele), Coffey, R.J. (Robert J), Cordeiro-da-Silva, A. (Anabela), Couch, Y. (Yvonne), Coumans, F.A.W. (Frank AW), Coyle, B. (Beth), Crescitelli, R. (Rossella), Criado, M.F. (Miria Ferreira), D’Souza-Schorey, C. (Crislyn), Das, S. (Saumya), de Candia, P. (Paola), De Santana, E.F. (Eliezer F), De Wever, O. (Olivier), Del Portillo, H. (Hernando), Demaret, T. (Tanguy), Deville, S. (Sarah), Devitt, A. (Andrew), Dhondt, B. (Bert), Di Vizio, D. (Dolores), Dieterich, L.C. (Lothar C), Dolo, V. (Vincenza), Dominguez Rubio, A.P. (Ana Paula), Dominici, M. (Massimo), Dourado, M.R. (Mauricio R), Driedonks, T.A.P. (Tom AP), Duarte, F.V. (Filipe V), Duncan, H.M. (Heather M), Eichenberger, R.M. (Ramon M), Ekström, K. (Karin), EL Andaloussi, S. (Samir), Elie-Caille, C. (Celine), Erdbrügger, U. (Uta), Falcon-Perez, J.M. (Juan), Fatima, F. (Farah), Fish, J.E. (Jason E), Flores-Bellver, M. (Miguel), Försönits, A. (András), Frelet-Barrand, A. (Annie), Fricke, F. (Fabia), Fuhrmann, G. (Gregor), Gabrielsson, S. (Susanne), Gámez-Valero, A. (Ana), Gardiner, C. (Chris), Gärtner, K. (Kathrin), Gaudin, R. (Raphael), Gho, Y.S. (Yong Song), Giebel, B. (B.), Gilbert, C. (Caroline), Gimona, M. (Mario), Giusti, I. (Ilaria), Goberdhan, D.C.I. (Deborah CI), Görgens, A. (André), Gorski, S.M. (Sharon M), Greening, D.W. (David W.), Gross, J.C. (Julia Christina), Gualerzi, A. (Alice), Gupta, G.N. (Gopal N), Gustafson, D. (Dakota), Handberg, A. (Aase), Haraszti, R.A. (Reka A), Harrison, P. (Paul), Hegyesi, H. (Hargita), Hendrix, A. (An), Hill, A.F. (Andrew F), Hochberg, F.H. (Fred H), Hoffmann, K.F. (Karl F), Holder, B. (Beth), Holthofer, H. (Harry), Hosseinkhani, B. (Baharak), Hu, G. (Guoku), Huang, Y. (Yiyao), Huber, V. (Veronica), Hunt, S. (Stuart), Ibrahim, A.G.-E. (Ahmed Gamal-Eldin), Ikezu, T. (Tsuneya), Inal, J.M. (Jameel), Isin, M. (Mustafa), Ivanova, A. (Alena), Jackson, H.K. (Hannah K), Jacobsen, S. (Soren), Jay, S.M. (Steven M), Jayachandran, M. (Muthuvel), Jenster, G.W. (Guido), Jiang, L. (Lanzhou), Johnson, S.M. (Suzanne M), Jones, J.C. (Jennifer C), Jong, A. (Ambrose), Jovanovic-Talisman, T. (Tijana), Jung, S. (Stephanie), Kalluri, R. (Raghu), Kano, S.-I. (Shin-ichi), Kaur, S. (Sukhbir), Kawamura, Y. (Yumi), Keller, E.T. (Evan T), Khamari, D. (Delaram), Khomyakova, E. (Elena), Khvorova, A. (Anastasia), Kierulf, P. (Peter), Kim, K.P. (Kwang Pyo), Kislinger, T. (Thomas), Klingeborn, M. (Mikael), Klinke, D.J. (David J), Kornek, M. (Miroslaw), Kosanović, M.M. (Maja M), Kovács, Á.F. (Árpád Ferenc), Krämer-Albers, E.-M. (Eva-Maria), Krasemann, S. (Susanne), Krause, M. (Mirja), Kurochkin, I.V. (Igor V), Kusuma, G.D. (Gina D), Kuypers, S. (Sören), Laitinen, S. (Saara), Langevin, S.M. (Scott M), Languino, L.R. (Lucia R), Lannigan, J. (Joanne), Lässer, C. (Cecilia), Laurent, L.C. (Louise C), Lavieu, G. (Gregory), Lázaro-Ibáñez, E. (Elisa), Le Lay, S. (Soazig), Lee, M.-S. (Myung-Shin), Lee, Y.X.F. (Yi Xin Fiona), Lemos, D.S. (Debora S), Lenassi, M. (Metka), Leszczynska, A. (Aleksandra), Li, I.T.S. (Isaac TS), Liao, K. (Ke), Libregts, S.F. (Sten), Ligeti, E. (Erzsebet), Lim, R. (Rebecca), Lim, S.K. (Sai Kiang), Linē, A. (Aija), Linnemannstöns, K. (Karen), Llorente, A. (Alicia), Lombard, C.A. (Catherine A), Lorenowicz, M.J. (Magdalena J), Lörincz, Á.M. (Ákos M), Lötvall, J. (Jan), Lovett, J. (Jason), Lowry, M.C. (Michelle C), Loyer, X. (Xavier), Lu, Q. (Quan), Lukomska, B. (Barbara), Lunavat, T.R. (Taral R), Maas, S.L.N. (Sybren), Malhi, H. (Harmeet), Marcilla, A. (Antonio), Mariani, J. (Jacopo), Mariscal, J. (Javier), Martens-Uzunova, E.S. (Elena), Martin-Jaular, L. (Lorena), Martinez, M.C. (M Carmen), Martins, V.R. (Vilma Regina), Mathieu, M. (Mathilde), Mathivanan, S. (Suresh), Maugeri, M. (Marco), McGinnis, L.K. (Lynda K), McVey, M.J. (Mark J), Meckes, D.G. (David G), Meehan, K.L. (Katie L), Mertens, I. (Inge), Minciacchi, V.R. (Valentina R), Möller, A. (Andreas), Møller Jørgensen, M. (Malene), Morales-Kastresana, A. (Aizea), Morhayim, J. (Jess), Mullier, F. (Francois), Muraca, M. (Maurizio), Musante, L. (Luca), Mussack, V. (Veronika), Muth, D.C. (Dillon C), Myburgh, K.H. (Kathryn H), Najrana, T. (Tanbir), Nawaz, M. (Muhammad), Nazarenko, I. (Irina), Nejsum, P. (Peter), Neri, C. (Christian), Neri, T. (Tommaso), Nieuwland, C.C.M. (Carolien) van, Nimrichter, L. (Leonardo), Nolan, J.P. (John P), Nolte-’t Hoen, E.N.M. (Esther NM), Hooten, N.N. (Nicole Noren), O’Driscoll, L. (Lorraine), O’Grady, T. (Tina), O’Loghlen, A. (Ana), Ochiya, T. (Takahiro), Olivier, M. (Martin), Ortiz, A. (Alberto), Ortiz, L.A. (Luis A), Osteikoetxea, X. (Xabier), Ostegaard, O. (Ole), Ostrowski, M. (Matias), Park, J. (Jaesung), Pegtel, D.M. (D. Michiel), Peinado, H. (Hector), Perut, F. (Francesca), Pfaffl, M.W. (Michael W), Phinney, D.G. (Donald G), Pieters, B.C.H. (Bartijn CH), Pink, R.C. (Ryan C), Pisetsky, D.S. (David S), Pogge von Strandmann, E. (Elke), Polakovicova, I. (Iva), Poon, I.K.H. (Ivan KH), Powell, B.H. (Bonita H), Prada, I. (Ilaria), Pulliam, L. (Lynn), Quesenberry, P. (Peter), Radeghieri, A. (Annalisa), Raffai, R.L. (Robert L), Raimondo, S. (Stefania), Rak, J. (Janusz), Ramirez, M.I. (Marcel I.), Raposo, L. (Luís), Rayyan, M.S. (Morsi S), Regev-Rudzki, N. (Neta), Ricklefs, F.L. (Franz L), Robbins, P.D. (Paul D), Roberts, D.D. (David D), Rodrigues, S.C. (Silvia C), Rohde, E. (Eva), Rome, S. (Sophie), Rouschop, K.M.A. (Kasper MA), Rughetti, A. (Aurelia), Russell, A.E. (Ashley E), Saá, P. (Paula), Sahoo, S. (Susmita), Salas-Huenuleo, E. (Edison), Sánchez, C. (Catherine), Saugstad, J.A. (Julie A), Saul, M.J. (Meike J), Schiffelers, R.M. (Raymond), Schneider, R. (Raphael), Schøyen, T.H. (Tine Hiorth), Scott, A. (Aaron), Shahaj, E. (Eriomina), Sharma, S. (Shivani), Shatnyeva, O. (Olga), Shekari, F. (Faezeh), Shelke, G.V. (Ganesh Vilas), Shetty, A.K. (Ashok K), Shiba, K. (Kiyotaka), Siljander, P. (Pia), Silva, A.M. (Andreia M), Skowronek, A. (Agata), Snyder, O.L. (Orman L), Soares, R.P. (Rodrigo Pedro), Sódar, B.W. (Barbara W), Soekmadji, C. (Carolina), Sotillo, J. (Javier), Stahl, P.D. (Philip D), Stoorvogel, W. (Willem), Stott, S.L. (Shannon L), Strasser, E.F. (Erwin F), Swift, S. (Simon), Tahara, H. (Hidetoshi), Tewari, M. (Muneesh), Timms, K. (Kate), Tiwari, S. (Swasti), Tixeira, R. (Rochelle), Tkach, M. (Mercedes), Toh, W.S. (Wei Seong), Tomasini, R. (Richard), Torrecilhas, A.C. (Ana Claudia), Tosar, J.P. (Juan Pablo), Toxavidis, V. (Vasilis), Urbanelli, L. (Lorena), Vader, P. (Pieter), Balkom, B.W.M. (Bas) van, van der Grein, S.G. (Susanne G), Van Deun, J. (Jan), van Herwijnen, M.J.C. (Martijn JC), Van Keuren-Jensen, K. (Kendall), van Niel, G. (Guillaume), Royen, M.E. (Martin), van Wijnen, A.J. (Andre J), Vasconcelos, M.H. (M Helena), Vechetti, I.J. (Ivan J), Veit, T.D. (Tiago D), Vella, L.J. (Laura J.), Velot, É. (Émilie), Verweij, F.J. (Frederik J), Vestad, B. (Beate), Viñas, J.L. (Jose L), Visnovitz, T. (Tamás), Vukman, K.V. (Krisztina V), Wahlgren, J. (Jessica), Watson, D.C. (Dionysios C), Wauben, M.H.M. (Marca), Weaver, A. (Alissa), Webber, J.P. (Jason P), Weber, V. (Viktoria), Wehman, A.M. (Ann M), Weiss, D.J. (Daniel J), Welsh, J.A. (Joshua A), Wendt, S. (Sebastian), Wheelock, A.M. (Asa M), Wiener, Z. (Zoltán), Witte, L. (Leonie), Wolfram, J. (Joy), Xagorari, A. (Angeliki), Xander, P. (Patricia), Xu, J. (Jing), Yan, X. (Xiaomei), Yáñez-Mó, M. (María), Yin, H. (Hang), Yuana, Y., Zappulli, V. (Valentina), Zarubova, J. (Jana), Žėkas, V. (Vytautas), Zhang, J.-Y. (Jian-ye), Zhao, Z. (Zezhou), Zheng, L. (Lei), Zheutlin, A.R. (Alexander R), Zickler, A.M. (Antje M), Zimmermann, P. (Pascale), Zivkovic, A.M. (Angela M), Zocco, D. (Davide), and Zuba-Surma, E.K. (Ewa K) more...
- Abstract
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make the more...
- Published
- 2019
- Full Text
- View/download PDF
17. The generation and use of recombinant extracellular vesicles as biological reference material
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Geeurickx, E. (Edward), Tulkens, J. (Joeri), Dhondt, B. (Bert), Van Deun, J. (Jan), Lippens, L. (Lien), Vergauwen, G. (Glenn), Heyrman, E. (Elisa), De Sutter, D. (Delphine), Gevaert, K. (Kris), Impens, F. (Francis), Miinalainen, I. (Ilkka), Van Bockstal, P.-J. (Pieter-Jan), De Beer, T. (Thomas), Wauben, M. H. (Marca H. M.), Nolte-‘t-Hoen, E. N. (Esther N. M.), Bloch, K. (Katarzyna), Swinnen, J. V. (Johannes V.), van der Pol, E. (Edwin), Nieuwland, R. (Rienk), Braems, G. (Geert), Callewaert, N. (Nico), Mestdagh, P. (Pieter), Vandesompele, J. (Jo), Denys, H. (Hannelore), Eyckerman, S. (Sven), De Wever, O. (Olivier), Hendrix, A. (An), Geeurickx, E. (Edward), Tulkens, J. (Joeri), Dhondt, B. (Bert), Van Deun, J. (Jan), Lippens, L. (Lien), Vergauwen, G. (Glenn), Heyrman, E. (Elisa), De Sutter, D. (Delphine), Gevaert, K. (Kris), Impens, F. (Francis), Miinalainen, I. (Ilkka), Van Bockstal, P.-J. (Pieter-Jan), De Beer, T. (Thomas), Wauben, M. H. (Marca H. M.), Nolte-‘t-Hoen, E. N. (Esther N. M.), Bloch, K. (Katarzyna), Swinnen, J. V. (Johannes V.), van der Pol, E. (Edwin), Nieuwland, R. (Rienk), Braems, G. (Geert), Callewaert, N. (Nico), Mestdagh, P. (Pieter), Vandesompele, J. (Jo), Denys, H. (Hannelore), Eyckerman, S. (Sven), De Wever, O. (Olivier), and Hendrix, A. (An) more...
- Abstract
Recent years have seen an increase of extracellular vesicle (EV) research geared towards biological understanding, diagnostics and therapy. However, EV data interpretation remains challenging owing to complexity of biofluids and technical variation introduced during sample preparation and analysis. To understand and mitigate these limitations, we generated trackable recombinant EV (rEV) as a biological reference material. Employing complementary characterization methods, we demonstrate that rEV are stable and bear physical and biochemical traits characteristic of sample EV. Furthermore, rEV can be quantified using fluorescence-, RNA- and protein-based technologies available in routine laboratories. Spiking rEV in biofluids allows recovery efficiencies of commonly implemented EV separation methods to be identified, intra-method and inter-user variability induced by sample handling to be defined, and to normalize and improve sensitivity of EV enumerations. We anticipate that rEV will aid EV-based sample preparation and analysis, data normalization, method development and instrument calibration in various research and biomedical applications. more...
- Published
- 2019
18. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines
- Author
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Thery, C, Witwer, KW, Aikawa, E, Jose Alcaraz, M, Anderson, JD, Andriantsitohaina, R, Antoniou, A, Arab, T, Archer, F, Atkin-Smith, GK, Ayre, DC, Bach, J-M, Bachurski, D, Baharvand, H, Balaj, L, Baldacchino, S, Bauer, NN, Baxter, AA, Bebawy, M, Beckham, C, Zavec, AB, Benmoussa, A, Berardi, AC, Bergese, P, Bielska, E, Blenkiron, C, Bobis-Wozowicz, S, Boilard, E, Boireau, W, Bongiovanni, A, Borras, FE, Bosch, S, Boulanger, CM, Breakefield, X, Breglio, AM, Brennan, MA, Brigstock, DR, Brisson, A, Broekman, MLD, Bromberg, JF, Bryl-Gorecka, P, Buch, S, Buck, AH, Burger, D, Busatto, S, Buschmann, D, Bussolati, B, Buzas, E, Byrd, JB, Camussi, G, Carter, DRF, Caruso, S, Chamley, LW, Chang, Y-T, Chen, C, Chen, S, Cheng, L, Chin, AR, Clayton, A, Clerici, SP, Cocks, A, Cocucci, E, Coffey, RJ, Cordeiro-da-Silva, A, Couch, Y, Coumans, FAW, Coyle, B, Crescitelli, R, Criado, MF, D'Souza-Schorey, C, Das, S, Chaudhuri, AD, de Candia, P, De Santana Junior, EF, De Wever, O, del Portillo, HA, Demaret, T, Deville, S, Devitt, A, Dhondt, B, Di Vizio, D, Dieterich, LC, Dolo, V, Dominguez Rubio, AP, Dominici, M, Dourado, MR, Driedonks, TAP, Duarte, F, Duncan, HM, Eichenberger, RM, Ekstrom, K, Andaloussi, SEL, Elie-Caille, C, Erdbrugger, U, Falcon-Perez, JM, Fatima, F, Fish, JE, Flores-Bellver, M, Forsonits, A, Frelet-Barrand, A, Fricke, F, Fuhrmann, G, Gabrielsson, S, Gamez-Valero, A, Gardiner, C, Gaertner, K, Gaudin, R, Gho, YS, Giebel, B, Gilbert, C, Gimona, M, Giusti, I, Goberdhan, DC, Goergens, A, Gorski, SM, Greening, DW, Gross, JC, Gualerzi, A, Gupta, GN, Gustafson, D, Handberg, A, Haraszti, RA, Harrison, P, Hegyesi, H, Hendrix, A, Hill, AF, Hochberg, FH, Hoffmann, KF, Holder, B, Holthofer, H, Hosseinkhani, B, Hu, G, Huang, Y, Huber, V, Hunt, S, Ibrahim, AG-E, Ikezu, T, Inal, JM, Isin, M, Ivanova, A, Jackson, HK, Jacobsen, S, Jay, SM, Jayachandran, M, Jenster, G, Jiang, L, Johnson, SM, Jones, JC, Jong, A, Jovanovic-Talisman, T, Jung, S, Kalluri, R, Kano, S-I, Kaur, S, Kawamura, Y, Keller, ET, Khamari, D, Khomyakova, E, Khvorova, A, Kierulf, P, Kim, KP, Kislinger, T, Klingeborn, M, Klinke, DJ, Kornek, M, Kosanovic, MM, Kovacs, AF, Kraemer-Albers, E-M, Krasemann, S, Krause, M, Kurochkin, I, Kusuma, GD, Kuypers, S, Laitinen, S, Langevin, SM, Languino, LR, Lannigan, J, Lasser, C, Laurent, LC, Lavieu, G, Lazaro-Ibanez, E, Le Lay, S, Lee, M-S, Lee, YXF, Lemos, DS, Lenassi, M, Leszczynska, A, Li, ITS, Liao, K, Libregts, SF, Ligeti, E, Lim, R, Lim, SK, Line, A, Linnemannstoens, K, Llorente, A, Lombard, CA, Lorenowicz, MJ, Lorincz, AM, Lotvall, J, Lovett, J, Lowry, MC, Loyer, X, Lu, Q, Lukomska, B, Lunavat, TR, Maas, SLN, Malhi, H, Marcilla, A, Mariani, J, Mariscal, J, Martens-Uzunova, ES, Martin-Jaular, L, Martinez, MC, Martins, VR, Mathieu, M, Mathivanan, S, Maugeri, M, McGinnis, LK, McVey, MJ, Meckes, DG, Meehan, KL, Mertens, I, Minciacchi, VR, Moller, A, Jorgensen, MM, Morales-Kastresana, A, Morhayim, J, Mullier, F, Muraca, M, Musante, L, Mussack, V, Muth, DC, Myburgh, KH, Najrana, T, Nawaz, M, Nazarenko, I, Nejsum, P, Neri, C, Neri, T, Nieuwland, R, Nimrichter, L, Nolan, JP, Nolte-'t Hoen, ENM, Noren Hooten, N, O'Driscoll, L, O'Grady, T, O'Loghlen, A, Ochiya, T, Olivier, M, Ortiz, A, Ortiz, LA, Osteikoetxea, X, Ostegaard, O, Ostrowski, M, Park, J, Pegtel, DM, Peinado, H, Perut, F, Pfaffl, MW, Phinney, DG, Pieters, BCH, Pink, RC, Pisetsky, DS, von Strandmann, EP, Polakovicova, I, Poon, IKH, Powell, BH, Prada, I, Pulliam, L, Quesenberry, P, Radeghieri, A, Raffai, RL, Raimondo, S, Rak, J, Ramirez, M, Raposo, G, Rayyan, MS, Regev-Rudzki, N, Ricklefs, FL, Robbins, PD, Roberts, DD, Rodrigues, SC, Rohde, E, Rome, S, Rouschop, KMA, Rughetti, A, Russell, AE, Saa, P, Sahoo, S, Salas-Huenuleo, E, Sanchez, C, Saugstad, JA, Saul, MJ, Schiffelers, RM, Schneider, R, Schoyen, TH, Scott, A, Shahaj, E, Sharma, S, Shatnyeva, O, Shekari, F, Shelke, GV, Shetty, AK, Shiba, K, Siljander, PR-M, Silva, AM, Skowronek, A, Snyder, OL, Soares, RP, Sodar, BW, Soekmadji, C, Sotillo, J, Stahl, PD, Stoorvogel, W, Stott, SL, Strasser, EF, Swift, S, Tahara, H, Tewari, M, Timms, K, Tiwari, S, Tixeira, R, Tkach, M, Toh, WS, Tomasini, R, Torrecilhas, AC, Pablo Tosar, J, Toxavidis, V, Urbanelli, L, Vader, P, van Balkom, BWM, van der Grein, SG, Van Deun, J, van Herwijnen, MJC, Van Keuren-Jensen, K, van Niel, G, van Royen, ME, van Wijnen, AJ, Helena Vasconcelos, M, Vechetti, IJ, Veit, TD, Vella, LJ, Velot, E, Verweij, FJ, Vestad, B, Vinas, JL, Visnovitz, T, Vukman, KV, Wahlgren, J, Watson, DC, Wauben, MHM, Weaver, A, Webber, JP, Weber, V, Wehman, AM, Weiss, DJ, Welsh, JA, Wendt, S, Wheelock, AM, Wiener, Z, Witte, L, Wolfram, J, Xagorari, A, Xander, P, Xu, J, Yan, X, Yanez-Mo, M, Yin, H, Yuana, Y, Zappulli, V, Zarubova, J, Zekas, V, Zhang, J-Y, Zhao, Z, Zheng, L, Zheutlin, AR, Zickler, AM, Zimmermann, P, Zivkovic, AM, Zocco, D, Zuba-Surma, EK, Thery, C, Witwer, KW, Aikawa, E, Jose Alcaraz, M, Anderson, JD, Andriantsitohaina, R, Antoniou, A, Arab, T, Archer, F, Atkin-Smith, GK, Ayre, DC, Bach, J-M, Bachurski, D, Baharvand, H, Balaj, L, Baldacchino, S, Bauer, NN, Baxter, AA, Bebawy, M, Beckham, C, Zavec, AB, Benmoussa, A, Berardi, AC, Bergese, P, Bielska, E, Blenkiron, C, Bobis-Wozowicz, S, Boilard, E, Boireau, W, Bongiovanni, A, Borras, FE, Bosch, S, Boulanger, CM, Breakefield, X, Breglio, AM, Brennan, MA, Brigstock, DR, Brisson, A, Broekman, MLD, Bromberg, JF, Bryl-Gorecka, P, Buch, S, Buck, AH, Burger, D, Busatto, S, Buschmann, D, Bussolati, B, Buzas, E, Byrd, JB, Camussi, G, Carter, DRF, Caruso, S, Chamley, LW, Chang, Y-T, Chen, C, Chen, S, Cheng, L, Chin, AR, Clayton, A, Clerici, SP, Cocks, A, Cocucci, E, Coffey, RJ, Cordeiro-da-Silva, A, Couch, Y, Coumans, FAW, Coyle, B, Crescitelli, R, Criado, MF, D'Souza-Schorey, C, Das, S, Chaudhuri, AD, de Candia, P, De Santana Junior, EF, De Wever, O, del Portillo, HA, Demaret, T, Deville, S, Devitt, A, Dhondt, B, Di Vizio, D, Dieterich, LC, Dolo, V, Dominguez Rubio, AP, Dominici, M, Dourado, MR, Driedonks, TAP, Duarte, F, Duncan, HM, Eichenberger, RM, Ekstrom, K, Andaloussi, SEL, Elie-Caille, C, Erdbrugger, U, Falcon-Perez, JM, Fatima, F, Fish, JE, Flores-Bellver, M, Forsonits, A, Frelet-Barrand, A, Fricke, F, Fuhrmann, G, Gabrielsson, S, Gamez-Valero, A, Gardiner, C, Gaertner, K, Gaudin, R, Gho, YS, Giebel, B, Gilbert, C, Gimona, M, Giusti, I, Goberdhan, DC, Goergens, A, Gorski, SM, Greening, DW, Gross, JC, Gualerzi, A, Gupta, GN, Gustafson, D, Handberg, A, Haraszti, RA, Harrison, P, Hegyesi, H, Hendrix, A, Hill, AF, Hochberg, FH, Hoffmann, KF, Holder, B, Holthofer, H, Hosseinkhani, B, Hu, G, Huang, Y, Huber, V, Hunt, S, Ibrahim, AG-E, Ikezu, T, Inal, JM, Isin, M, Ivanova, A, Jackson, HK, Jacobsen, S, Jay, SM, Jayachandran, M, Jenster, G, Jiang, L, Johnson, SM, Jones, JC, Jong, A, Jovanovic-Talisman, T, Jung, S, Kalluri, R, Kano, S-I, Kaur, S, Kawamura, Y, Keller, ET, Khamari, D, Khomyakova, E, Khvorova, A, Kierulf, P, Kim, KP, Kislinger, T, Klingeborn, M, Klinke, DJ, Kornek, M, Kosanovic, MM, Kovacs, AF, Kraemer-Albers, E-M, Krasemann, S, Krause, M, Kurochkin, I, Kusuma, GD, Kuypers, S, Laitinen, S, Langevin, SM, Languino, LR, Lannigan, J, Lasser, C, Laurent, LC, Lavieu, G, Lazaro-Ibanez, E, Le Lay, S, Lee, M-S, Lee, YXF, Lemos, DS, Lenassi, M, Leszczynska, A, Li, ITS, Liao, K, Libregts, SF, Ligeti, E, Lim, R, Lim, SK, Line, A, Linnemannstoens, K, Llorente, A, Lombard, CA, Lorenowicz, MJ, Lorincz, AM, Lotvall, J, Lovett, J, Lowry, MC, Loyer, X, Lu, Q, Lukomska, B, Lunavat, TR, Maas, SLN, Malhi, H, Marcilla, A, Mariani, J, Mariscal, J, Martens-Uzunova, ES, Martin-Jaular, L, Martinez, MC, Martins, VR, Mathieu, M, Mathivanan, S, Maugeri, M, McGinnis, LK, McVey, MJ, Meckes, DG, Meehan, KL, Mertens, I, Minciacchi, VR, Moller, A, Jorgensen, MM, Morales-Kastresana, A, Morhayim, J, Mullier, F, Muraca, M, Musante, L, Mussack, V, Muth, DC, Myburgh, KH, Najrana, T, Nawaz, M, Nazarenko, I, Nejsum, P, Neri, C, Neri, T, Nieuwland, R, Nimrichter, L, Nolan, JP, Nolte-'t Hoen, ENM, Noren Hooten, N, O'Driscoll, L, O'Grady, T, O'Loghlen, A, Ochiya, T, Olivier, M, Ortiz, A, Ortiz, LA, Osteikoetxea, X, Ostegaard, O, Ostrowski, M, Park, J, Pegtel, DM, Peinado, H, Perut, F, Pfaffl, MW, Phinney, DG, Pieters, BCH, Pink, RC, Pisetsky, DS, von Strandmann, EP, Polakovicova, I, Poon, IKH, Powell, BH, Prada, I, Pulliam, L, Quesenberry, P, Radeghieri, A, Raffai, RL, Raimondo, S, Rak, J, Ramirez, M, Raposo, G, Rayyan, MS, Regev-Rudzki, N, Ricklefs, FL, Robbins, PD, Roberts, DD, Rodrigues, SC, Rohde, E, Rome, S, Rouschop, KMA, Rughetti, A, Russell, AE, Saa, P, Sahoo, S, Salas-Huenuleo, E, Sanchez, C, Saugstad, JA, Saul, MJ, Schiffelers, RM, Schneider, R, Schoyen, TH, Scott, A, Shahaj, E, Sharma, S, Shatnyeva, O, Shekari, F, Shelke, GV, Shetty, AK, Shiba, K, Siljander, PR-M, Silva, AM, Skowronek, A, Snyder, OL, Soares, RP, Sodar, BW, Soekmadji, C, Sotillo, J, Stahl, PD, Stoorvogel, W, Stott, SL, Strasser, EF, Swift, S, Tahara, H, Tewari, M, Timms, K, Tiwari, S, Tixeira, R, Tkach, M, Toh, WS, Tomasini, R, Torrecilhas, AC, Pablo Tosar, J, Toxavidis, V, Urbanelli, L, Vader, P, van Balkom, BWM, van der Grein, SG, Van Deun, J, van Herwijnen, MJC, Van Keuren-Jensen, K, van Niel, G, van Royen, ME, van Wijnen, AJ, Helena Vasconcelos, M, Vechetti, IJ, Veit, TD, Vella, LJ, Velot, E, Verweij, FJ, Vestad, B, Vinas, JL, Visnovitz, T, Vukman, KV, Wahlgren, J, Watson, DC, Wauben, MHM, Weaver, A, Webber, JP, Weber, V, Wehman, AM, Weiss, DJ, Welsh, JA, Wendt, S, Wheelock, AM, Wiener, Z, Witte, L, Wolfram, J, Xagorari, A, Xander, P, Xu, J, Yan, X, Yanez-Mo, M, Yin, H, Yuana, Y, Zappulli, V, Zarubova, J, Zekas, V, Zhang, J-Y, Zhao, Z, Zheng, L, Zheutlin, AR, Zickler, AM, Zimmermann, P, Zivkovic, AM, Zocco, D, and Zuba-Surma, EK more...
- Abstract
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points. more...
- Published
- 2018
19. Confounding factors of ultrafiltration and protein analysis in extracellular vesicle research
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Vergauwen, G. (Glenn), Dhondt, B. (Bert), Van Deun, J. (Jan), De Smedt, E. (Eva), Berx, G. (Geert), Timmerman, E. (Evy), Gevaert, K. (Kris), Miinalainen, I. (Ilkka), Cocquyt, V. (Véronique), Braems, G. (Geert), Van den Broecke, R. (Rudy), Denys, H. (Hannelore), De Wever, O. (Olivier), Hendrix, A. (An), Vergauwen, G. (Glenn), Dhondt, B. (Bert), Van Deun, J. (Jan), De Smedt, E. (Eva), Berx, G. (Geert), Timmerman, E. (Evy), Gevaert, K. (Kris), Miinalainen, I. (Ilkka), Cocquyt, V. (Véronique), Braems, G. (Geert), Van den Broecke, R. (Rudy), Denys, H. (Hannelore), De Wever, O. (Olivier), and Hendrix, A. (An) more...
- Abstract
Identification and validation of extracellular vesicle (EV)-associated biomarkers requires robust isolation and characterization protocols. We assessed the impact of some commonly implemented pre-analytical, analytical and post-analytical variables in EV research. Centrifugal filters with different membrane types and pore sizes are used to reduce large volume biofluids prior to EV isolation or to concentrate EVs. We compared five commonly reported filters for their efficiency when using plasma, urine and EV-spiked PBS. Regenerated cellulose membranes with pore size of 10 kDa recovered EVs the most efficient. Less than 40% recovery was achieved with other filters. Next, we analyzed the effect of the type of protein assays to measure EV protein in colorimetric and fluorometric kits. The fluorometric assay Qubit measured low concentration EV and BSA samples the most accurately with the lowest variation among technical and biological replicates. Lastly, we quantified Optiprep remnants in EV samples from density gradient ultracentrifugation and demonstrate that size-exclusion chromatography efficiently removes Optiprep from EVs. In conclusion, choice of centrifugal filters and protein assays confound EV analysis and should be carefully considered to increase efficiency towards biomarker discovery. SEC-based removal of Optiprep remnants from EVs can be considered for downstream applications. more...
- Published
- 2017
20. The transcriptome of lung tumor-infiltrating dendritic cells reveals a tumor-supporting phenotype and a microRNA signature with negative impact on clinical outcome
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Pyfferoen, L, Brabants, E, Everaert, C, De Cabooter, N, Heyns, K, Deswarte, K, Vanheerswynghels, M, De Prijck, S, Waegemans, G, Dullaers, M, Hammad, H, De Wever, O, Mestdagh, P, Vandesompele, J, Lambrecht, Bart, Vermaelen, KY, Pyfferoen, L, Brabants, E, Everaert, C, De Cabooter, N, Heyns, K, Deswarte, K, Vanheerswynghels, M, De Prijck, S, Waegemans, G, Dullaers, M, Hammad, H, De Wever, O, Mestdagh, P, Vandesompele, J, Lambrecht, Bart, and Vermaelen, KY more...
- Published
- 2017
21. 154P - Splenic metabolic activity as biomarker in cervical cancer
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De Jaeghere, E.A., Laloo, F., Lippens, L., De Man, K., Van Bockstal, M., Van de Vijver, K., Tummers, P., Makar, A., De Visschere, P., De Wever, O., Amant, F., Denys, H., and Vandecasteele, K.
- Published
- 2019
- Full Text
- View/download PDF
22. APOBEC3G expression correlates with T-cell infiltration and improved clinical outcomes in high-grade serous ovarian carcinoma
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Leonard, B. (Brandon), Starrett, G.J. (Gabriel J.), Maurer, M.J. (Matthew J.), Oberg, A.L. (Ann L.), Van Bockstal, M. (Mieke), Van Dorpe, J. (Jo), De Wever, O. (Olivier), Helleman, J. (Jozien), Sieuwerts, A.M. (Anieta), Berns, P.M.J.J. (Els), Martens, J.W.M. (John), Anderson, B.D. (Brett D.), Brown, W.L. (William L.), Kalli, K.R. (Kimberly R.), Kaufmann, S.H. (Scott H.), Harris, R.S. (Reuben), Leonard, B. (Brandon), Starrett, G.J. (Gabriel J.), Maurer, M.J. (Matthew J.), Oberg, A.L. (Ann L.), Van Bockstal, M. (Mieke), Van Dorpe, J. (Jo), De Wever, O. (Olivier), Helleman, J. (Jozien), Sieuwerts, A.M. (Anieta), Berns, P.M.J.J. (Els), Martens, J.W.M. (John), Anderson, B.D. (Brett D.), Brown, W.L. (William L.), Kalli, K.R. (Kimberly R.), Kaufmann, S.H. (Scott H.), and Harris, R.S. (Reuben) more...
- Abstract
__Purpose:__ APOBEC3 DNA cytosine deaminase family members normally defend against viruses and transposons. However, deregulated APOBEC3 activity causes mutations in cancer. Because of broad expression profiles and varying mixtures of normal and cancer cells in tumors, including immune cell infiltration, it is difficult to determine where different APOBEC3s are expressed. Here, we ask whether correlations exist between APOBEC3 expression and T-cell infiltration in high-grade serous ovarian cancer (HGSOC), and assess whether these correlations have prognostic value. __Experimental Design:__ Transcripts for APOBEC3G, APOBEC3B, and the T-cell markers, CD3D, CD4, CD8A, GZMB, PRF1, and RNF128 were quantified by RT-qPCR for a cohort of 354 HGSOC patients. Expression values were correlated with each other and clinical parameters. Two additional cohorts were used to extend HGSOC clinical results. Immunoimaging was used to colocalize APOBEC3G and the T-cell marker CD3. TCGA data extended expression analyses to additional cancer types. __Results:__ A surprising positive correlation was found for expression of APOBEC3G and several T cell genes in HGSOC. Immunohistochemistry and immunofluorescent imaging showed protein colocalization in tumor-infiltrating T lymphocytes. High APOBEC3G expression correlated with improved outcomes in multiple HGSOC cohorts. TCGA data analyses revealed that expression of APOBEC3D and APOBEC3H also correlates with CD3D across multiple cancer types. __Conclusions:__ Our results identify APOBEC3G as a new candidate biomarker for tumor-infiltrating T lymphocytes and favorable prognoses for HGSOC. Our data also highlight the complexity of the tumor environment with respect to differential APOBEC family gene expression in both tumor and surrounding normal cell types. Clin Cancer Res; 22(18); 4746-55. more...
- Published
- 2016
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23. Fibroblast activation protein-α, a stromal cell surface protease, shapes key features of cancer associated fibroblasts through proteome and degradome alterations
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Koczorowska, M.M., primary, Tholen, S., additional, Bucher, F., additional, Lutz, L., additional, Kizhakkedathu, J.N., additional, De Wever, O., additional, Wellner, U.F., additional, Biniossek, M.L., additional, Stahl, A., additional, Lassmann, S., additional, and Schilling, O., additional more...
- Published
- 2015
- Full Text
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24. Effect of the secretory small GTPases Rab27B on breast cancer growth, invasion, and metastasis
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Hendrix, A., Maynard, D., Pauwels, P., Braems, G., Denys, H., Van den Broecke, R., Lambert, J., Van Belle, S., Cocquyt, V., Gespach, C., Bracke, M., Seabra, MC., Gahl, WA., De Wever, O., and Westbroek, W. more...
- Subjects
EXPRESSION ,GRISCELLI-SYNDROME ,MATRIX METALLOPROTEINASES ,HEPATOCELLULAR-CARCINOMA ,EXOCYTOSIS ,GRANULES ,SHOCK-PROTEIN 90 ,HSP90 ,MASS-SPECTROMETRY ,CELL-MIGRATION - Abstract
Methods Expression of green fluorescent protein (GFP) fused with wild-type Rab3D, Rab27A, or Rab27B, or Rab27B point mutants defective in GTP/GDP binding or geranylgeranylation, or transient silencing RNA to the same proteins was used to study Rab27B in estrogen receptor (ER)-positive human breast cancer cell lines (MCF-7, T47D, and ZR75.1). Cell cycle progression was evaluated by flow cytometry, western blotting, and measurement of cell proliferation rates, and invasion was assessed using Matrigel and native type I collagen substrates. Orthotopic tumor growth, local invasion, and metastasis were analyzed in mouse xenograft models. Mass spectrometry identified proinvasive growth regulators that were secreted in the presence of Rab27B. Rab27B protein levels were evaluated by immunohistochemistry in 59 clinical breast cancer specimens, and Rab3D, Rab27A, and Rab27B mRNA levels were analyzed by quantitative real-time polymerase chain reaction in 20 specimens. Statistical tests were two-sided. more...
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- 2010
25. Stromal protein expression in breast cancer is differentially regulated by TGF-&bgr;1
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Van Bockstal, M., primary, Lambein, K., additional, Van Gele, M., additional, De Vlieghere, E., additional, Limame, R., additional, Braems, G., additional, Bracke, M., additional, Denys, H., additional, Libbrecht, L., additional, and De Wever, O., additional more...
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- 2015
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26. Expression of the small GTPase Rab27B is associated with stromal inflammation in ductal carcinoma in situ of the breast
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Van Bockstal, M., primary, Lambein, K., additional, De Wever, O., additional, Denys, H., additional, Braems, G., additional, Van den Broecke, R., additional, Cocquyt, V.F.J., additional, Bracke, M., additional, Libbrecht, L., additional, and Hendrix, A., additional more...
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- 2015
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27. The secretory small GTPase Rab27B as a marker for breast cancer progression
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Hendrix A, Braems G, Bracke M, Miguel Seabra, Gahl W, De Wever O, and Westbroek W
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EXPRESSION ,MELANOCYTES ,GRISCELLI-SYNDROME ,PROTEINS ,Breast Neoplasms ,Prognosis ,GENE ,Gene Expression Regulation, Neoplastic ,Oncology ,Receptors, Estrogen ,rab GTP-Binding Proteins ,Lymphatic Metastasis ,METASTASIS ,CELLS ,Biomarkers, Tumor ,Disease Progression ,Medicine and Health Sciences ,Humans ,GROWTH ,Female ,Neoplasm Invasiveness ,Research Perspectives ,Signal Transduction - Abstract
In contemporary oncology practice, an urgent need remains to refine the prognostic assessment of breast cancer. It is still difficult to identify patients with early breast cancer who are likely to benefit from adjuvant chemotherapy. Although invasion of cancer cells is the main prognostic denominator in tumor malignancy, our molecular understanding and diagnosis are often inadequate to cope with this activity. Therefore, deciphering molecular pathways of how tumors invade and metastasize may help in the identification of a useful prognostic marker. We recently discovered that the secretory small GTPase Rab27B, a regulator of vesicle exocytosis, delivers proinvasive signals for increased invasiveness, tumor size, and metastasis of various estrogen receptor (ER)-positive breast cancer cell lines, both in vitro and in vivo. In human breast cancer specimens, the presence of Rab27B protein proved to be associated with a low degree of differentiation and the presence of lymph node metastasis in ER-positive breast cancer. more...
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- 2010
28. Stromal Characteristics are Potential Prognostic Markers for Ipsilateral Locoregional Recurrence in Ductal Carcinoma in Situ (DCIS)
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Van Bockstal, M., primary, Lambein, K., additional, De Wever, O., additional, Praet, M., additional, Cocquyt, V., additional, Van den Broecke, R., additional, Braems, G., additional, Denys, H., additional, and Libbrecht, L., additional more...
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- 2014
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29. Epithelial expression of FHL2 is negatively associated with metastasis-free and overall survival in colorectal cancer
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Verset, L, primary, Tommelein, J, additional, Moles Lopez, X, additional, Decaestecker, C, additional, Mareel, M, additional, Bracke, M, additional, Salmon, I, additional, De Wever, O, additional, and Demetter, P, additional more...
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- 2013
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30. JAK3 deregulation by activating mutations confers invasive growth advantage in extranodal nasal-type natural killer cell lymphoma
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Bouchekioua, A, primary, Scourzic, L, additional, de Wever, O, additional, Zhang, Y, additional, Cervera, P, additional, Aline-Fardin, A, additional, Mercher, T, additional, Gaulard, P, additional, Nyga, R, additional, Jeziorowska, D, additional, Douay, L, additional, Vainchenker, W, additional, Louache, F, additional, Gespach, C, additional, Solary, E, additional, and Coppo, P, additional more...
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- 2013
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31. 81P - Expression of the small GTPase Rab27B is associated with stromal inflammation in ductal carcinoma in situ of the breast
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Van Bockstal, M., Lambein, K., De Wever, O., Denys, H., Braems, G., Van den Broecke, R., Cocquyt, V.F.J., Bracke, M., Libbrecht, L., and Hendrix, A.
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- 2015
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32. 80P - Stromal protein expression in breast cancer is differentially regulated by TGF-&bgr;1
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Van Bockstal, M., Lambein, K., Van Gele, M., De Vlieghere, E., Limame, R., Braems, G., Bracke, M., Denys, H., Libbrecht, L., and De Wever, O.
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- 2015
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33. Invasion and MMP expression profile in desmoid tumours
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Denys, H, primary, De Wever, O, additional, Nusgens, B, additional, Kong, Y, additional, Sciot, R, additional, Le, A-T, additional, Van Dam, K, additional, Jadidizadeh, A, additional, Tejpar, S, additional, Mareel, M, additional, Alman, B, additional, and Cassiman, J-J, additional more...
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- 2004
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34. 25P - Stromal Characteristics are Potential Prognostic Markers for Ipsilateral Locoregional Recurrence in Ductal Carcinoma in Situ (DCIS)
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Van Bockstal, M., Lambein, K., De Wever, O., Praet, M., Cocquyt, V., Van den Broecke, R., Braems, G., Denys, H., and Libbrecht, L.
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- 2014
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35. Role of the focal adhesion protein kindlin-1 in breast cancer growth and lung metastasis.
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Sin S, Bonin F, Petit V, Meseure D, Lallemand F, Bièche I, Bellahcène A, Castronovo V, de Wever O, Gespach C, Lidereau R, and Driouch K
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- 2011
36. Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines
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Théry, Clotilde, Witwer, Kenneth W, Aikawa, Elena, Alcaraz, Maria Jose, Anderson, Johnathon D, Andriantsitohaina, Ramaroson, Antoniou, Anna, Arab, Tanina, Archer, Fabienne, Atkin-Smith, Georgia K, Ayre, D Craig, Bach, Jean-Marie, Bachurski, Daniel, Baharvand, Hossein, Balaj, Leonora, Baldacchino, Shawn, Bauer, Natalie N, Baxter, Amy A, Bebawy, Mary, Beckham, Carla, Bedina Zavec, Apolonija, Benmoussa, Abderrahim, Berardi, Anna C, Bergese, Paolo, Bielska, Ewa, Blenkiron, Cherie, Bobis-Wozowicz, Sylwia, Boilard, Eric, Boireau, Wilfrid, Bongiovanni, Antonella, Borràs, Francesc E, Bosch, Steffi, Boulanger, Chantal M, Breakefield, Xandra, Breglio, Andrew M, Brennan, Meadhbh Á, Brigstock, David R, Brisson, Alain, Broekman, Marike Ld, Bromberg, Jacqueline F, Bryl-Górecka, Paulina, Buch, Shilpa, Buck, Amy H, Burger, Dylan, Busatto, Sara, Buschmann, Dominik, Bussolati, Benedetta, Buzás, Edit I, Byrd, James Bryan, Camussi, Giovanni, Carter, David Rf, Caruso, Sarah, Chamley, Lawrence W, Chang, Yu-Ting, Chen, Chihchen, Chen, Shuai, Cheng, Lesley, Chin, Andrew R, Clayton, Aled, Clerici, Stefano P, Cocks, Alex, Cocucci, Emanuele, Coffey, Robert J, Cordeiro-da-Silva, Anabela, Couch, Yvonne, Coumans, Frank Aw, Coyle, Beth, Crescitelli, Rossella, Criado, Miria Ferreira, D'Souza-Schorey, Crislyn, Das, Saumya, Datta Chaudhuri, Amrita, de Candia, Paola, De Santana, Eliezer F, De Wever, Olivier, Del Portillo, Hernando A, Demaret, Tanguy, Deville, Sarah, Devitt, Andrew, Dhondt, Bert, Di Vizio, Dolores, Dieterich, Lothar C, Dolo, Vincenza, Dominguez Rubio, Ana Paula, Dominici, Massimo, Dourado, Mauricio R, Driedonks, Tom Ap, Duarte, Filipe V, Duncan, Heather M, Eichenberger, Ramon M, Ekström, Karin, El Andaloussi, Samir, Elie-Caille, Celine, Erdbrügger, Uta, Falcón-Pérez, Juan M, Fatima, Farah, Fish, Jason E, Flores-Bellver, Miguel, Försönits, András, Frelet-Barrand, Annie, Fricke, Fabia, Fuhrmann, Gregor, Gabrielsson, Susanne, Gámez-Valero, Ana, Gardiner, Chris, Gärtner, Kathrin, Gaudin, Raphael, Gho, Yong Song, Giebel, Bernd, Gilbert, Caroline, Gimona, Mario, Giusti, Ilaria, Goberdhan, Deborah Ci, Görgens, André, Gorski, Sharon M, Greening, David W, Gross, Julia Christina, Gualerzi, Alice, Gupta, Gopal N, Gustafson, Dakota, Handberg, Aase, Haraszti, Reka A, Harrison, Paul, Hegyesi, Hargita, Hendrix, An, Hill, Andrew F, Hochberg, Fred H, Hoffmann, Karl F, Holder, Beth, Holthofer, Harry, Hosseinkhani, Baharak, Hu, Guoku, Huang, Yiyao, Huber, Veronica, Hunt, Stuart, Ibrahim, Ahmed Gamal-Eldin, Ikezu, Tsuneya, Inal, Jameel M, Isin, Mustafa, Ivanova, Alena, Jackson, Hannah K, Jacobsen, Soren, Jay, Steven M, Jayachandran, Muthuvel, Jenster, Guido, Jiang, Lanzhou, Johnson, Suzanne M, Jones, Jennifer C, Jong, Ambrose, Jovanovic-Talisman, Tijana, Jung, Stephanie, Kalluri, Raghu, Kano, Shin-Ichi, Kaur, Sukhbir, Kawamura, Yumi, Keller, Evan T, Khamari, Delaram, Khomyakova, Elena, Khvorova, Anastasia, Kierulf, Peter, Kim, Kwang Pyo, Kislinger, Thomas, Klingeborn, Mikael, Klinke, David J, Kornek, Miroslaw, Kosanović, Maja M, Kovács, Árpád Ferenc, Krämer-Albers, Eva-Maria, Krasemann, Susanne, Krause, Mirja, Kurochkin, Igor V, Kusuma, Gina D, Kuypers, Sören, Laitinen, Saara, Langevin, Scott M, Languino, Lucia R, Lannigan, Joanne, Lässer, Cecilia, Laurent, Louise C, Lavieu, Gregory, Lázaro-Ibáñez, Elisa, Le Lay, Soazig, Lee, Myung-Shin, Lee, Yi Xin Fiona, Lemos, Debora S, Lenassi, Metka, Leszczynska, Aleksandra, Li, Isaac Ts, Liao, Ke, Libregts, Sten F, Ligeti, Erzsebet, Lim, Rebecca, Lim, Sai Kiang, Linē, Aija, Linnemannstöns, Karen, Llorente, Alicia, Lombard, Catherine A, Lorenowicz, Magdalena J, Lörincz, Ákos M, Lötvall, Jan, Lovett, Jason, Lowry, Michelle C, Loyer, Xavier, Lu, Quan, Lukomska, Barbara, Lunavat, Taral R, Maas, Sybren Ln, Malhi, Harmeet, Marcilla, Antonio, Mariani, Jacopo, Mariscal, Javier, Martens-Uzunova, Elena S, Martin-Jaular, Lorena, Martinez, M Carmen, Martins, Vilma Regina, Mathieu, Mathilde, Mathivanan, Suresh, Maugeri, Marco, McGinnis, Lynda K, McVey, Mark J, Meckes, David G, Meehan, Katie L, Mertens, Inge, Minciacchi, Valentina R, Möller, Andreas, Møller Jørgensen, Malene, Morales-Kastresana, Aizea, Morhayim, Jess, Mullier, François, Muraca, Maurizio, Musante, Luca, Mussack, Veronika, Muth, Dillon C, Myburgh, Kathryn H, Najrana, Tanbir, Nawaz, Muhammad, Nazarenko, Irina, Nejsum, Peter, Neri, Christian, Neri, Tommaso, Nieuwland, Rienk, Nimrichter, Leonardo, Nolan, John P, Nolte-'t Hoen, Esther NM, Noren Hooten, Nicole, O'Driscoll, Lorraine, O'Grady, Tina, O'Loghlen, Ana, Ochiya, Takahiro, Olivier, Martin, Ortiz, Alberto, Ortiz, Luis A, Osteikoetxea, Xabier, Østergaard, Ole, Ostrowski, Matias, Park, Jaesung, Pegtel, D Michiel, Peinado, Hector, Perut, Francesca, Pfaffl, Michael W, Phinney, Donald G, Pieters, Bartijn Ch, Pink, Ryan C, Pisetsky, David S, Pogge von Strandmann, Elke, Polakovicova, Iva, Poon, Ivan Kh, Powell, Bonita H, Prada, Ilaria, Pulliam, Lynn, Quesenberry, Peter, Radeghieri, Annalisa, Raffai, Robert L, Raimondo, Stefania, Rak, Janusz, Ramirez, Marcel I, Raposo, Graça, Rayyan, Morsi S, Regev-Rudzki, Neta, Ricklefs, Franz L, Robbins, Paul D, Roberts, David D, Rodrigues, Silvia C, Rohde, Eva, Rome, Sophie, Rouschop, Kasper Ma, Rughetti, Aurelia, Russell, Ashley E, Saá, Paula, Sahoo, Susmita, Salas-Huenuleo, Edison, Sánchez, Catherine, Saugstad, Julie A, Saul, Meike J, Schiffelers, Raymond M, Schneider, Raphael, Schøyen, Tine Hiorth, Scott, Aaron, Shahaj, Eriomina, Sharma, Shivani, Shatnyeva, Olga, Shekari, Faezeh, Shelke, Ganesh Vilas, Shetty, Ashok K, Shiba, Kiyotaka, Siljander, Pia R-M, Silva, Andreia M, Skowronek, Agata, Snyder, Orman L, Soares, Rodrigo Pedro, Sódar, Barbara W, Soekmadji, Carolina, Sotillo, Javier, Stahl, Philip D, Stoorvogel, Willem, Stott, Shannon L, Strasser, Erwin F, Swift, Simon, Tahara, Hidetoshi, Tewari, Muneesh, Timms, Kate, Tiwari, Swasti, Tixeira, Rochelle, Tkach, Mercedes, Toh, Wei Seong, Tomasini, Richard, Torrecilhas, Ana Claudia, Tosar, Juan Pablo, Toxavidis, Vasilis, Urbanelli, Lorena, Vader, Pieter, van Balkom, Bas Wm, van der Grein, Susanne G, Van Deun, Jan, van Herwijnen, Martijn Jc, Van Keuren-Jensen, Kendall, van Niel, Guillaume, van Royen, Martin E, van Wijnen, Andre J, Vasconcelos, M Helena, Vechetti, Ivan J, Veit, Tiago D, Vella, Laura J, Velot, Émilie, Verweij, Frederik J, Vestad, Beate, Viñas, Jose L, Visnovitz, Tamás, Vukman, Krisztina V, Wahlgren, Jessica, Watson, Dionysios C, Wauben, Marca Hm, Weaver, Alissa, Webber, Jason P, Weber, Viktoria, Wehman, Ann M, Weiss, Daniel J, Welsh, Joshua A, Wendt, Sebastian, Wheelock, Asa M, Wiener, Zoltán, Witte, Leonie, Wolfram, Joy, Xagorari, Angeliki, Xander, Patricia, Xu, Jing, Yan, Xiaomei, Yáñez-Mó, María, Yin, Hang, Yuana, Yuana, Zappulli, Valentina, Zarubova, Jana, Žėkas, Vytautas, Zhang, Jian-Ye, Zhao, Zezhou, Zheng, Lei, Zheutlin, Alexander R, Zickler, Antje M, Zimmermann, Pascale, Zivkovic, Angela M, Zocco, Davide, Zuba-Surma, Ewa K, dB&C I&I, LS Celbiologie-Algemeen, Celbiologie, Afd Pharmaceutics, Sub General Pharmaceutics, Sub Biomol.Mass Spect. and Proteomics, Afd Pharmacology, Urology, Pathology, Medical Oncology, Immunité et cancer, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Johns Hopkins University School of Medicine [Baltimore], Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Immuno-Endocrinologie Cellulaire et Moléculaire [Nantes] (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Department for Molecular Biology and Nanobiotechnology, National Institute of chemitry, Slovenia, Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole 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Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Imagerie Moléculaire et Nanobiotechnologies - Institut Européen de Chimie et Biologie (IECB), Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), Molecular Biotechnology Center, Università degli studi di Torino = University of Turin (UNITO), Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Centre for Sustainable Tropical Fisheries and Aquaculture, James Cook University (JCU), Department of Oncology - Pathology, Cancer Center Karolinska [Karolinska Institutet] (CCK), Karolinska Institutet [Stockholm]-Karolinska Institutet [Stockholm], Departamento de Ciências Biológicas, Universidade do Porto = University of Porto, Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent (CRIG), Universiteit Gent = Ghent University [Belgium] (UGENT), Department of Medical and Surgical Sciences for Children and Adults [Modena, Italy] (Laboratory of Cellular Therapy), Università degli Studi di Modena e Reggio Emilia (UNIMORE), Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Center for Cooperative Research in Biosciences (CIC bioGUNE), Partner site Munich, German Centre for Infection Research (DZIF), Institute for Transfusion Medicine, University Hospital Essen, Universität Duisburg-Essen [Essen], Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Psychiatry, Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Department of Bacteriology and Immunology [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Dalhousie University [Halifax], Department of Biology, Molecular Cell Biology, University of Mainz, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Glycobiologie et signalisation cellulaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg (GU), Universidad de Alicante, École supérieure du professorat et de l'éducation - Académie de Créteil (UPEC ESPE Créteil), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Antwerp (UA), Université Catholique de Louvain = Catholic University of Louvain (UCL), Research Institute, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Department of Veterinary Disease Biology [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Biologie et Pathologie du Neurone (Brain-C), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Mathematics and Statistics, American University, University of Pretoria [South Africa], Ecole des Ingénieurs de la Ville de Paris (EIVP), Universitat Pompeu Fabra [Barcelona] (UPF), Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México (UNAM), Istituto Ortopedico Rizzoli, Department of Molecular Therapeutics, The Scripps Research Institute, Laboratoire d'Informatique de Grenoble (LIG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Montreal Children's Hospital, McGill University Health Center [Montreal] (MUHC), Compartimentation et dynamique cellulaires (CDC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Research Center, Massachusetts General Hospital [Boston], University Medical Center [Utrecht], University of Toronto, Fiocruz Minas - René Rachou Research Center / Instituto René Rachou [Belo Horizonte, Brésil], Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Federal University of Sao Paulo (Unifesp), Functional Genomics / Genómica Funcional [Montevideo], Institut Pasteur de Montevideo, Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università degli Studi di Perugia (UNIPG), Hospital Santa Cristina Instituto de Investigación Sanitaria Princesa C, Unidad de Investigación, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology, University of California [San Francisco] (UCSF), University of California-University of California, University of Vermont [Burlington], Peking University [Beijing], Shandong Agricultural University (SDAU), State Key Laboratory of Quality Research in Chinese Medicine Taipa, Macau SAR, (Institute of Chinese Medical Sciences), Human Genetics, Universität Ulm - Ulm University [Ulm, Allemagne], INSERM, Institut Curie, INCa [INCA-11548], French National Research Agency [ANR-10-IDEX-0001-02 PSL*, ANR-11-LABX-0043], SIDACTION [17-1-AAE-1138], Fondation ARC [PGA1 RF20180206962, PJA 20171206453], NIDA [DA040385, DA047807], Ministry of Education, NIA [AG057430], NIMH [MH118164], Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University (UGENT), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Biotechnology and Biological Sciences Research Council (BBSRC)-Aberystwyth University, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), The Scripps Research Institute [La Jolla, San Diego], Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Università degli Studi di Perugia = University of Perugia (UNIPG), Instituto de Investigacion Sanitaria del Hospital de la Princesa, Hospital Universitario de La Princesa, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), ANR-17-CE09-0025,MADNESS,Une approche microfluidique générique pour la qualification des nanoparticules biologiques(2017), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, Laboratory Specialized Diagnostics & Research, Radiotherapie, RS: GROW - R2 - Basic and Translational Cancer Biology, Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Università degli studi di Torino (UNITO), Universidade do Porto, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Johannes Gutenberg - Universität Mainz (JGU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université de Toronto [Canada], Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192 (PRISM), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade do Porto [Porto], Ghent University [Belgium] (UGENT), FEMTO-ST Institute, Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Franche-Comté (UFC)-CNRS : UMR6174, Mécanismes adaptatifs : des organismes aux communautés (MECADEV), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN), Johannes Gutenberg - University of Mainz (JGU), Université Catholique de Louvain (UCL), Universitat Pompeu Fabra [Barcelona], Laboratoire d'Informatique de Grenoble (LIG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire Réactions et Génie des Procédés (LRGP), Fiocruz Minas - René Rachou Research Center / Instituto René Rachou, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Functional Genomics Unit, Institut Curie-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Vermont College of Medicine [Burlington, VT, USA], Extracellular Vesicles, Molecular and Integrative Biosciences Research Programme, Thery, C., Witwer, K. W., Aikawa, E., Alcaraz, M. J., Anderson, J. D., Andriantsitohaina, R., Antoniou, A., Arab, T., Archer, F., Atkin-Smith, G. K., Ayre, D. C., Bach, J. -M., Bachurski, D., Baharvand, H., Balaj, L., Baldacchino, S., Bauer, N. N., Baxter, A. A., Bebawy, M., Beckham, C., Bedina Zavec, A., Benmoussa, A., Berardi, A. C., Bergese, P., Bielska, E., Blenkiron, C., Bobis-Wozowicz, S., Boilard, E., Boireau, W., Bongiovanni, A., Borras, F. E., Bosch, S., Boulanger, C. M., Breakefield, X., Breglio, A. M., Brennan, M. A., Brigstock, D. R., Brisson, A., Broekman, M. L. D., Bromberg, J. F., Bryl-Gorecka, P., Buch, S., Buck, A. H., Burger, D., Busatto, S., Buschmann, D., Bussolati, B., Buzas, E. I., Byrd, J. B., Camussi, G., Carter, D. R. F., Caruso, S., Chamley, L. W., Chang, Y. -T., Chaudhuri, A. D., Chen, C., Chen, S., Cheng, L., Chin, A. R., Clayton, A., Clerici, S. P., Cocks, A., Cocucci, E., Coffey, R. J., Cordeiro-da-Silva, A., Couch, Y., Coumans, F. A. W., Coyle, B., Crescitelli, R., Criado, M. F., D'Souza-Schorey, C., Das, S., de Candia, P., De Santana, E. F., De Wever, O., del Portillo, H. A., Demaret, T., Deville, S., Devitt, A., Dhondt, B., Di Vizio, D., Dieterich, L. C., Dolo, V., Dominguez Rubio, A. P., Dominici, M., Dourado, M. R., Driedonks, T. A. P., Duarte, F. V., Duncan, H. M., Eichenberger, R. M., Ekstrom, K., EL Andaloussi, S., Elie-Caille, C., Erdbrugger, U., Falcon-Perez, J. M., Fatima, F., Fish, J. E., Flores-Bellver, M., Forsonits, A., Frelet-Barrand, A., Fricke, F., Fuhrmann, G., Gabrielsson, S., Gamez-Valero, A., Gardiner, C., Gartner, K., Gaudin, R., Gho, Y. S., Giebel, B., Gilbert, C., Gimona, M., Giusti, I., Goberdhan, D. C. I., Gorgens, A., Gorski, S. M., Greening, D. W., Gross, J. C., Gualerzi, A., Gupta, G. N., Gustafson, D., Handberg, A., Haraszti, R. A., Harrison, P., Hegyesi, H., Hendrix, A., Hill, A. F., Hochberg, F. H., Hoffmann, K. F., Holder, B., Holthofer, H., Hosseinkhani, B., Hu, G., Huang, Y., Huber, V., Hunt, S., Ibrahim, A. G. -E., Ikezu, T., Inal, J. M., Isin, M., Ivanova, A., Jackson, H. K., Jacobsen, S., Jay, S. M., Jayachandran, M., Jenster, G., Jiang, L., Johnson, S. M., Jones, J. C., Jong, A., Jovanovic-Talisman, T., Jung, S., Kalluri, R., Kano, S. -I., Kaur, S., Kawamura, Y., Keller, E. T., Khamari, D., Khomyakova, E., Khvorova, A., Kierulf, P., Kim, K. P., Kislinger, T., Klingeborn, M., Klinke, D. J., Kornek, M., Kosanovic, M. M., Kovacs, A. F., Kramer-Albers, E. -M., Krasemann, S., Krause, M., Kurochkin, I. V., Kusuma, G. D., Kuypers, S., Laitinen, S., Langevin, S. M., Languino, L. R., Lannigan, J., Lasser, C., Laurent, L. C., Lavieu, G., Lazaro-Ibanez, E., Le Lay, S., Lee, M. -S., Lee, Y. X. F., Lemos, D. S., Lenassi, M., Leszczynska, A., Li, I. T. S., Liao, K., Libregts, S. F., Ligeti, E., Lim, R., Lim, S. K., Line, A., Linnemannstons, K., Llorente, A., Lombard, C. A., Lorenowicz, M. J., Lorincz, A. M., Lotvall, J., Lovett, J., Lowry, M. C., Loyer, X., Lu, Q., Lukomska, B., Lunavat, T. R., Maas, S. L. N., Malhi, H., Marcilla, A., Mariani, J., Mariscal, J., Martens-Uzunova, E. S., Martin-Jaular, L., Martinez, M. C., Martins, V. R., Mathieu, M., Mathivanan, S., Maugeri, M., Mcginnis, L. K., Mcvey, M. J., Meckes, D. G., Meehan, K. L., Mertens, I., Minciacchi, V. R., Moller, A., Moller Jorgensen, M., Morales-Kastresana, A., Morhayim, J., Mullier, F., Muraca, M., Musante, L., Mussack, V., Muth, D. C., Myburgh, K. H., Najrana, T., Nawaz, M., Nazarenko, I., Nejsum, P., Neri, C., Neri, T., Nieuwland, R., Nimrichter, L., Nolan, J. P., Nolte-'t Hoen, E. N. M., Noren Hooten, N., O'Driscoll, L., O'Grady, T., O'Loghlen, A., Ochiya, T., Olivier, M., Ortiz, A., Ortiz, L. A., Osteikoetxea, X., Ostegaard, O., Ostrowski, M., Park, J., Pegtel, D. M., Peinado, H., Perut, F., Pfaffl, M. W., Phinney, D. G., Pieters, B. C. H., Pink, R. C., Pisetsky, D. S., Pogge von Strandmann, E., Polakovicova, I., Poon, I. K. H., Powell, B. H., Prada, I., Pulliam, L., Quesenberry, P., Radeghieri, A., Raffai, R. L., Raimondo, S., Rak, J., Ramirez, M. I., Raposo, G., Rayyan, M. S., Regev-Rudzki, N., Ricklefs, F. L., Robbins, P. D., Roberts, D. D., Rodrigues, S. C., Rohde, E., Rome, S., Rouschop, K. M. A., Rughetti, A., Russell, A. E., Saa, P., Sahoo, S., Salas-Huenuleo, E., Sanchez, C., Saugstad, J. A., Saul, M. J., Schiffelers, R. M., Schneider, R., Schoyen, T. H., Scott, A., Shahaj, E., Sharma, S., Shatnyeva, O., Shekari, F., Shelke, G. V., Shetty, A. K., Shiba, K., Siljander, P. R. -M., Silva, A. M., Skowronek, A., Snyder, O. L., Soares, R. P., Sodar, B. W., Soekmadji, C., Sotillo, J., Stahl, P. D., Stoorvogel, W., Stott, S. L., Strasser, E. F., Swift, S., Tahara, H., Tewari, M., Timms, K., Tiwari, S., Tixeira, R., Tkach, M., Toh, W. S., Tomasini, R., Torrecilhas, A. C., Tosar, J. P., Toxavidis, V., Urbanelli, L., Vader, P., van Balkom, B. W. M., van der Grein, S. G., Van Deun, J., van Herwijnen, M. J. C., Van Keuren-Jensen, K., van Niel, G., van Royen, M. E., van Wijnen, A. J., Vasconcelos, M. H., Vechetti, I. J., Veit, T. D., Vella, L. J., Velot, E., Verweij, F. J., Vestad, B., Vinas, J. L., Visnovitz, T., Vukman, K. V., Wahlgren, J., Watson, D. C., Wauben, M. H. M., Weaver, A., Webber, J. P., Weber, V., Wehman, A. M., Weiss, D. J., Welsh, J. A., Wendt, S., Wheelock, A. M., Wiener, Z., Witte, L., Wolfram, J., Xagorari, A., Xander, P., Xu, J., Yan, X., Yanez-Mo, M., Yin, H., Yuana, Y., Zappulli, V., Zarubova, J., Zekas, V., Zhang, J. -Y., Zhao, Z., Zheng, L., Zheutlin, A. R., Zickler, A. M., Zimmermann, P., Zivkovic, A. M., Zocco, D., Zuba-Surma, E. K., dB&C I&I, LS Celbiologie-Algemeen, Celbiologie, Afd Pharmaceutics, Sub General Pharmaceutics, Sub Biomol.Mass Spect. and Proteomics, Afd Pharmacology, CCA - Imaging and biomarkers, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Amsterdam Neuroscience - Cellular & Molecular Mechanisms more...
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ectosome ,ectosomes ,exosomes ,extracellular vesicles ,guidelines ,microparticles ,microvesicles ,minimal information requirements ,reproducibility ,rigor ,standardization ,Histology ,Cell Biology ,[SDV]Life Sciences [q-bio] ,size-exclusion ,Medicine and Health Sciences ,CELL-DERIVED MICROPARTICLES ,FIELD-FLOW FRACTIONATION ,requirements ,circulating ,ComputingMilieux_MISCELLANEOUS ,Manchester Cancer Research Centre ,lcsh:Cytology ,PROSTATE-CANCER ,microparticle ,Cell interaction ,microvesicle ,chromatography ,Position Paper ,guideline ,Life Sciences & Biomedicine ,ectosomes, exosomes, extracellular vesicles, guidelines, microparticles, microvesicles, minimal information requirements, reproducibility, rigor, standardization ,MEMBRANE-VESICLES ,FETAL BOVINE ,Ectosomes ,Exosomes ,Extracellular Vesicles ,Guidelines ,Microparticles ,Microvesicles ,Minimal Information Requirements ,Reproducibility ,Rigor ,Standardization ,CIRCULATING MICROPARTICLES ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,ddc:570 ,exosome ,SURFACE-PLASMON RESONANCE ,ddc:610 ,lcsh:QH573-671 ,Biology ,Interacció cel·lular ,Science & Technology ,ResearchInstitutes_Networks_Beacons/mcrc ,Cell membranes ,HUMAN URINARY EXOSOMES ,PREANALYTICAL PARAMETERS ,minimal information requirement ,SIZE-EXCLUSION CHROMATOGRAPHY ,1182 Biochemistry, cell and molecular biology ,extracellular vesicle ,Human medicine ,Membranes cel·lulars - Abstract
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points. more...
- Published
- 2018
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37. EV-TRACK: transparent reporting and centralizing knowledge in extracellular vesicle research
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Eva De Smedt, Bieke Soen, Marta Monguió-Tortajada, Jasper Anckaert, Erminia Romano, Els Beghein, Hina Kalra, Alessandra Lo Cicero, Michael W. Pfaffl, Laurence Bertier, Bert Dhondt, Edward Geeurickx, Özden Akay, Lorraine O'Driscoll, Frederik J. Verweij, Alan Van Goethem, Dominik Buschmann, Olivier De Wever, Zoraida Andreu Martinez, Susanne G. van der Grein, Carina Leonelli, Vincent Hyenne, Shu Liu, Prabhu Mathiyalagan, Guillaume van Niel, Andrew D Foers, Niels Vandamme, Joeri Tulkens, Petra Leidinger, Jan Van Deun, James Brian Byrd, Suzanne Vanhauwaert, David Kim, Patrizia Agostinis, Seyma Demirsoy, Esther N. M. Nolte-‘t Hoen, Stephanie Boukouris, Aleksandra M. Dudek, Michel Bremer, Anna Cmoch, Sandra Kraemer, Kathrin Gärtner, Clotilde Théry, Hetty Helsmoortel, Farzaneh Ghazavi, Pieter Mestdagh, Dillon C. Muth, Jo Vandesompele, Grace V. Hancock, Lien Lippens, Tom Groot Kormelink, Tom A. P. Driedonks, Abdou ElSharawy, Sushma Anand, Marijke I. Zonneveld, Benjamin J. Scicluna, Joanna Kowal, Susmita Sahoo, Lesley Cheng, Safia Thaminy, Isabel Van Audenhove, Suresh Mathivanan, Ilaria Floris, Glenn Vergauwen, Geert Berx, Jan Gettemans, Johannes V. Swinnen, Yaxuan Liang, Victoria Depoorter, Shaun Martin, Alexander R. van Vliet, Natalia G. Sampaio, Martijn J. C. van Herwijnen, Bernd Giebel, Abhishek D. Garg, Bjarke Primdal-Bengtson, An Hendrix, Gloria Milani, Tamás Matusek, Liselot Mus, Annelynn Wallaert, Andrew F. Hill, Roberta Palmulli, Maarit Takatalo, Tine Baetens, Clara Casert, Janneke Boere, Monisha Samuel, Marca H. M. Wauben, Nadine Van Roy, Delphine Daveloose, Anneleen Steels, Andrea Németh, Kenneth W. Witwer, Quentin Rousseau, Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent (CRIG), Universiteit Gent = Ghent University [Belgium] (UGENT), Center for Medical Genetics, Cancer Research Institute Ghent (CRIG), Bioinformatics Institute Ghent (BIG), Cell Death Research & Therapy (CDRT) Lab, Université Catholique de Louvain = Catholic University of Louvain (UCL), Molecular and Cellular Oncology Lab, Inflammation Research Center, VIB, Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Hospital Santa Cristina Instituto de Investigación Sanitaria Princesa C, Unidad de Investigación, Department of Biochemistry, Faculty of Medicine and Health Sciences, Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University [Utrecht], Institute for Transfusion Medicine, University Hospital Essen, Universität Duisburg-Essen [Essen], Animal Physiology and Immunology, School of Life Sciences, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Laboratory of Cytometry, Department of Internal Medicine, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of Biochemistry, Hôpital Lapeyronie, Institute of Clinical Molecular Biology, Kiel University, Faculty of Sciences, Division of Biochemistry, Chemistry Department, Damietta University, Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Department of Biochemistry, Microbiology and Immunology, University of Ottawa [Ottawa], Inflammation Division, The Walter and Eliza Hall Institute of Medical Research (WEHI), Department of Medical Biology, Hacettepe University Faculty of Medicine, Partner site Munich, German Centre for Infection Research (DZIF), Research Unit Gene Vectors, Helmholtz-Zentrum München (HZM), Department of Molecular and Comparative Pathobiology and Department of Neurology, Johns Hopkins University School of Medicine, Fédération de Médecine Translationelle de Strasbourg (FMTS), LabEx Medalis, Université de Strasbourg (UNISTRA), U1109, MN3T, Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Research Center, Massachusetts General Hospital [Boston], Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Department of Thoracic and Cardiovascular Surgery, University Hospital RWTH Aachen, Institute of Human Genetics, Universität Ulm - Ulm University [Ulm, Allemagne], German Center for Neurodegenerative Diseases, Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), REMAR-IVECAT Group, Germans Trias i Pujol Health Science Research Institute, Department of Genetics, Cell- and Immunobiology, Semmelweis University, School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Population Health and Immunity Division, Laboratory of Lipid Metabolism and Cancer, Department of Oncology, LKI - Leuven Cancer Institute, Faculty of Biological and Environmental Sciences [Helsinki], University of Helsinki, Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, National Cancer Center, Fund for Scientific Spearheads of the Ghent University Hospital, Concerted Research Actions from Ghent University, Stichting tegen Kanker, Kom Op Tegen Kanker, H2020/COST ME-HaD, Fund for Scientific Research Flanders (FWO), Krediet aan Navorsers from FWO, Universiteit Gent = Ghent University (UGENT), Instituto de Investigacion Sanitaria del Hospital de la Princesa, Hospital Universitario de La Princesa, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Helmholtz Zentrum München = German Research Center for Environmental Health, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Van Deun J., Mestdagh P., Agostinis P., Akay O., Anand S., Anckaert J., Martinez Z.A., Baetens T., Beghein E., Bertier L., Berx G., Boere J., Boukouris S., Bremer M., Buschmann D., Byrd J.B., Casert C., Cheng L., Cmoch A., Daveloose D., De Smedt E., Demirsoy S., Depoorter V., Dhondt B., Driedonks T.A.P., Dudek A., Elsharawy A., Floris I., Foers A.D., Gartner K., Garg A.D., Geeurickx E., Gettemans J., Ghazavi F., Giebel B., Kormelink T.G., Hancock G., Helsmoortel H., Hill A.F., Hyenne V., Kalra H., Kim D., Kowal J., Kraemer S., Leidinger P., Leonelli C., Liang Y., Lippens L., Liu S., Lo Cicero A., Martin S., Mathivanan S., Mathiyalagan P., Matusek T., Milani G., Monguio-Tortajada M., Mus L.M., Muth D.C., Nemeth A., Nolte-'T Hoen E.N.M., O'Driscoll L., Palmulli R., Pfaffl M.W., Primdal-Bengtson B., Romano E., Rousseau Q., Sahoo S., Sampaio N., Samuel M., Scicluna B., Soen B., Steels A., Swinnen J.V., Takatalo M., Thaminy S., Thery C., Tulkens J., Van Audenhove I., Van Der Grein S., Van Goethem A., Van Herwijnen M.J., Van Niel G., Van Roy N., Van Vliet A.R., Vandamme N., Vanhauwaert S., Vergauwen G., Verweij F., Wallaert A., Wauben M., Witwer K.W., Zonneveld M.I., De Wever O., Vandesompele J., Hendrix A., Ghent University [Belgium] (UGENT), Université Catholique de Louvain, Technical University of Munich (TUM), Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), University of Ottawa [Ottawa] (uOttawa), Walter and Eliza Hall Institute of Medical Research (WEHI), Institut Curie-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), PSL Research University (PSL), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), and Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA) more...
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0301 basic medicine ,minimum information ,blood-plasma ,physiology [Extracellular Vesicles] ,Biomedical Research ,Internationality ,Computer science ,phenotype ,[SDV]Life Sciences [q-bio] ,Medizin ,exosomes ,Crowdsourcing ,Bioinformatics ,Biochemistry ,03 medical and health sciences ,Extracellular Vesicles ,ultracentrifugation ,Biological property ,cancer ,ddc:610 ,resolution flow-cytometry ,Molecular Biology ,subpopulations ,business.industry ,biological-properties ,Cell Biology ,Extracellular vesicle ,Data science ,Databases, Bibliographic ,Replication (computing) ,030104 developmental biology ,cells ,business ,Biotechnology - Abstract
We argue that the field of extracellular vesicle (EV) biology needs more transparent reporting to facilitate interpretation and replication of experiments. To achieve this, we describe EV-TRACK, a crowdsourcing knowledgebase (http://evtrack.org) that centralizes EV biology and methodology with the goal of stimulating authors, reviewers, editors and funders to put experimental guidelines into practice. more...
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- 2017
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38. Biological properties of extracellular vesicles and their physiological functions
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Juan M. Falcón-Pérez, Irene M. Ghobrial, Aija Linē, Eva Rohde, Francesco Cappello, Irina Nazarenko, María Yáñez-Mó, Saara Laitinen, Mayda Gursel, María Mittelbrunn, Krisztina Buzas, Mario Gimona, Erzsébet Ligeti, An Hendrix, Ihsan Gursel, Marie Stampe Ostenfeld, Antonio Marcilla, Joana Carvalho, Eva-Maria Krämer-Albers, Georg Lipps, Francisco Sánchez-Madrid, Thomas Lener, Carla Oliveira, Éva Pállinger, Francesc E. Borràs, Susanne G. van der Grein, Olivier De Wever, Veronika Kralj-Iglič, Bernd Giebel, Anabela Cordeiro da Silva, Esther N. M. Nolte-‘t Hoen, Nuno Santarém, Willem Stoorvogel, Marina Rigau, Hernando A. del Portillo, Katsutoshi Kokubun, Marca H. M. Wauben, Alicia Llorente, Apolonija Bedina Zavec, Eva Colas, Katharina Schallmoser, Maja Kosanović, Peter Kierulf, Jaume Reventós, Mireia Olivan, Jan Lötvall, Edit I. Buzás, Enriqueta Casal, Michael W. Graner, Pia Siljander, Stefano Fais, Cecilia Lässer, Marei Sammar, Niels H. H. Heegaard, Lorraine O'Driscoll, Roman Štukelj, Tuula A. Nyman, Zoraida Andreu, Mateja Manček-Keber, M. Helena Vasconcelos, Infection & Immunity, Fertility & Reproduction, dB&C I&I, LS Celbiologie-Algemeen, Yanez-Mo M., Siljander P.R.-M., Andreu Z., Zavec A.B., Borras F.E., Buzas E.I., Buzas K., Casal E., Cappello F., Carvalho J., Colas E., Cordeiro-Da Silva A., Fais S., Falcon-Perez J.M., Ghobrial I.M., Giebel B., Gimona M., Graner M., Gursel I., Gursel M., Heegaard N.H.H., Hendrix A., Kierulf P., Kokubun K., Kosanovic M., Kralj-Iglic V., Kramer-Albers E.-M., Laitinen S., Lasser C., Lener T., Ligeti E., Line A., Lipps G., Llorente A., Lotvall J., Mancek-Keber M., Marcilla A., Mittelbrunn M., Nazarenko I., Nolte-'t Hoen E.N.M., Nyman T.A., O'Driscoll L., Olivan M., Oliveira C., Pallinger E., Del Portillo H.A., Reventos J., Rigau M., Rohde E., Sammar M., Sanchez-Madrid F., Santarem N., Schallmoser K., Ostenfeld M.S., Stoorvogel W., Stukelj R., Van Der Grein S.G., Helena Vasconcelos M., Wauben M.H.M., and De Wever O. more...
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Proteomics ,Cellular distribution ,MATURE DENDRITIC CELLS ,Review ,Review Article ,Urine ,Embryo development ,Monocyte ,Protein processing ,Vascular biology ,Feces ,Vesícules seminals ,SYNCYTIOTROPHOBLAST MICROVILLOUS MEMBRANES ,Cell selection ,Pregnancy ,T lymphocyte ,Bile ,CELL-DERIVED EXOSOMES ,Biogenesis ,Lung lavage ,Uterus fluid ,Innate immunity ,Male genital system ,lcsh:Cytology ,Microvesicle ,OUTER-MEMBRANE VESICLES ,Blood clotting ,prokaryote ,Eukaryota ,Extracellular vesicle ,RNA analysis ,Cell biology ,Blood ,Cerebrospinal fluid ,Liver metabolism ,microvesicle ,Morphogen ,Human ,Nervous system ,Cell signaling ,Breast milk ,Natural killer cell ,Fisiologia ,Extracellular vesicles ,Exosome ,lcsh:QH573-671 ,Saliva ,Biology ,Biology and Life Sciences ,DNA ,Plant ,RNA transport ,Cell function ,Macrophage ,Molecular biology ,Physiology ,Medizin ,FACTOR PATHWAY INHIBITOR ,eukaryote ,Protein glycosylation ,Extracellular space ,Tissue repair ,Espai extracel·lular ,Reticulocyte ,Seminal plasma ,Mesenchymal stem cell ,Antigen presenting cell ,Seminal vesicles ,Nose mucus ,Biofilm ,Neutrophil ,MicroRNA ,PLANT-MICROBE INTERACTIONS ,Lipid ,Amnion fluid ,Prokaryota ,microparticle ,Cell interaction ,Cell transport ,eukaryote, exosome, extracellular vesicle, microparticle, microvesicle, physiology, prokaryote ,Bone mineralization ,Microorganism ,Histology ,Adaptive immunity ,Membrane vesicle ,Computational biology ,Membrane receptor ,Stress ,Cell communication ,Mast cell ,MESENCHYMAL STEM-CELLS ,HUMAN ENDOTHELIAL-CELLS ,exosome ,Cytokine ,Synovial fluid ,Cell Biology ,Nonhuman ,IMMUNE-MODULATORY FEATURES ,Review article ,DNA content ,physiology ,RNA ,INTESTINAL EPITHELIAL-CELLS ,extracellular vesicle ,Body fluid ,Lectin - Abstract
The authors wish to thank Dr R Simpson and Dr D Taylor for critical reading of the manuscript and acknowledge the Horizon 2020 European Cooperation in Science and Technology programme and its support of our European Network on Microvesicles and Exosomes in Health & Disease (ME-HaD; BM1202 www.cost.eu/COST_Actions/bmbs/Actions/BM1202). In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system. more...
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- 2015
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39. Correction: Pembrolizumab, radiotherapy, and an immunomodulatory five-drug cocktail in pretreated patients with persistent, recurrent, or metastatic cervical or endometrial carcinoma: Results of the phase II PRIMMO study.
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De Jaeghere EA, Tuyaerts S, Van Nufel AMT, Belmans A, Bogaerts K, Baiden-Amissah R, Lippens L, Vuylsteke P, Henry S, Trinh XB, van Dam PA, Aspeslagh S, De Caluwé A, Naert E, Lambrechts D, Hendrix A, De Wever O, Van de Vijver KK, Amant F, Vandecasteele K, and Denys HG more...
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- 2024
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40. Pelophen B is a non-taxoid binding microtubule-stabilizing agent with promising preclinical anticancer properties.
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Vermeulen S, Ernst S, Blondeel E, Xia Z, Rappu P, Heino J, Dedeyne S, Denys H, Sys G, Gijsels S, Depypere H, Tummers P, Ceelen W, Craciun L, Demetter P, Raes O, Hendrix A, Van der Eycken J, and De Wever O more...
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- Humans, Cell Line, Tumor, Drug Resistance, Neoplasm drug effects, Animals, G2 Phase Cell Cycle Checkpoints drug effects, Cell Survival drug effects, Lactones pharmacology, Lactones chemistry, Lactones metabolism, Tubulin Modulators pharmacology, Tubulin Modulators chemistry, Microtubules metabolism, Microtubules drug effects, Paclitaxel pharmacology, Tubulin metabolism, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry
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Taxanes, such as paclitaxel (PTX), stabilize microtubules and are used as a first-line therapy in multiple cancer types. Disruption of microtubule equilibrium, which plays an essential role in mitosis and cell homeostasis, ultimately results in cell death. Even though PTX is a very potent chemotherapy, its use is associated with major side effects and therapy resistance. Pelophen B (PPH), a synthetic analog of peloruside A, stabilizes microtubules through interaction with a non-taxoid binding site of β-tubulin. We evaluated the anticancer effect of PPH in a variety of tumor types by using established cell lines, early-passage cultures and ex vivo tumor-derived cultures that preserve the 3D architecture of the tumor microenvironment. PPH significantly blocks colony formation capacity, reduces viability and exerts additivity with PTX. Interestingly, PPH overcomes resistance to PTX. Mechanistically, PPH induces a G2/M cell cycle arrest and increases the presence of tubulin polymerization promoting protein (TPPP), inducing lysine 40 acetylation of α-tubulin. Although, results induced by paclitaxel or PPH are concordant, PPH's unique microtubule binding mechanism enables PTX additivity and ensures overcoming PTX-induced resistance. In conclusion, PPH results in remarkable anti-cancer activity in a range of preclinical models supporting further clinical investigation of PPH as a therapeutic anticancer agent., Competing Interests: Declarations. Competing interests: Johan Vander Eycken is patentholder of Pelophen B (PCT/EP2014/075903). All other authors declare no competing interests. Ethics approval and consent to participate: Informed consent of patients to use tumor material was obtained after the study protocol was approved by the institutional review board of the Ghent University Hospital (EC 2018/0080 and ONZ-2022–0345, EC 2019/1869 and ONZ-2023-0502). All animal experiments were approved by the local ethics committee (ECD 19-45 and ECD 19-86, Ghent University Hospital). All animal experiments were conducted in accordance with the regulatory guidelines of the Ethics Committee of Ghent University Hospital and the ARRIVE guidelines., (© 2024. The Author(s).) more...
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- 2024
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41. Mapping bacterial extracellular vesicle research: insights, best practices and knowledge gaps.
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De Langhe N, Van Dorpe S, Guilbert N, Vander Cruyssen A, Roux Q, Deville S, Dedeyne S, Tummers P, Denys H, Vandekerckhove L, De Wever O, and Hendrix A
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- Humans, Extracellular Vesicles metabolism, Bacteria metabolism
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Bacterial extracellular vesicles (BEVs) enable communication between bacteria and their natural habitats, including multicellular organisms such as humans. Consequently, the study of BEVs has rapidly gained attention with recent research raising the prospect of developing BEVs as biomarkers and treatments to manage (mal)functioning of natural habitats. Although diverse technologies are available, the composition of their source, their heterogeneity in biophysical and biochemical features, and their multifaceted cargo composition challenges the analysis of BEVs. To map current practices in BEV research, we analyzed 845 publications released in 2015-2021, reporting 3338 BEV-related experiments. The extracted data are accessible via the publicly available EV-TRACK knowledgebase ( https://evtrack.org/ ). We identify the need for transparent reporting, delineate knowledge gaps, outline available best practices and define areas in need of guidance to ensure advances in BEV research and accelerate BEV applications., (© 2024. The Author(s).) more...
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- 2024
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42. Dual-ligand PROTACS mediate superior target protein degradation in vitro and therapeutic efficacy in vivo .
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Chen Y, Xia Z, Suwal U, Rappu P, Heino J, De Wever O, and De Geest BG
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Proteolysis targeting chimeras (PROTACs) are revolutionizing the drug development landscape due to their unique ability to selectively degrade disease-associated proteins. Conventional PROTACs are bivalent entities that induce ubiquitination and subsequent proteolysis of a chosen protein of interest (POI) by forming a ternary complex with an E3 ligase. We hypothesized that dual-ligand PROTACs, featuring two copies each of a POI ligand and an E3 ligase ligand, would facilitate the formation of high-avidity, long-lived ternary complexes inside cells, thereby increasing POI degradation potency. To this end, we developed a convergent synthesis route, using l-aspartic acid as a building block for homodimer synthesis, followed by copper-catalyzed azide-alkyne cycloaddition (CuAAC) to conjugate both dimers through a flexible linker. Dual-ligand PROTACs achieved up to a tenfold increase in degradation efficiency and a hundredfold increase in cytotoxicity in vitro across various cancer cell lines compared to their single-ligand counterparts. Furthermore, dual-ligand PROTACs sustain prolonged protein degradation, up to 60 hours after pulsing and washout. In vivo , in a mouse tumor model, the superior therapeutic activity of dual ligand PROTACs was observed., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.) more...
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- 2024
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43. Cancer-associated fibroblasts mediate resistance to neoadjuvant therapy in breast cancer.
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Xia Z, Vermeulen S, Suwal U, Rappu P, Heino J, De Vuyst F, Dedeyne S, Hendrix A, Denys H, and De Wever O
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- Humans, Female, Breast Neoplasms drug therapy, Neoadjuvant Therapy methods, Cancer-Associated Fibroblasts drug effects, Cancer-Associated Fibroblasts metabolism, Drug Resistance, Neoplasm drug effects
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- 2024
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44. Zebrafish Avatars: Toward Functional Precision Medicine in Low-Grade Serous Ovarian Cancer.
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Fieuws C, Bek JW, Parton B, De Neef E, De Wever O, Hoorne M, Estrada MF, Van Dorpe J, Denys H, Van de Vijver K, and Claes KBM
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Ovarian cancer (OC) is an umbrella term for cancerous malignancies affecting the ovaries, yet treatment options for all subtypes are predominantly derived from high-grade serous ovarian cancer, the largest subgroup. The concept of "functional precision medicine" involves gaining personalized insights on therapy choice, based on direct exposure of patient tissues to drugs. This especially holds promise for rare subtypes like low-grade serous ovarian cancer (LGSOC). This study aims to establish an in vivo model for LGSOC using zebrafish embryos, comparing treatment responses previously observed in mouse PDX models, cell lines and 3D tumor models. To address this goal, a well-characterized patient-derived LGSOC cell line with the KRAS mutation c.35 G>T (p.(Gly12Val)) was used. Fluorescently labeled tumor cells were injected into the perivitelline space of 2 days' post-fertilization zebrafish embryos. At 1 day post-injection, xenografts were assessed for tumor size, followed by random allocation into treatment groups with trametinib, luminespib and trametinib + luminespib. Subsequently, xenografts were euthanized and analyzed for apoptosis and proliferation by confocal microscopy. Tumor cells formed compact tumor masses ( n = 84) in vivo, with clear Ki67 staining, indicating proliferation. Zebrafish xenografts exhibited sensitivity to trametinib and luminespib, individually or combined, within a two-week period, establishing them as a rapid and complementary tool to existing in vitro and in vivo models for evaluating targeted therapies in LGSOC. more...
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- 2024
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45. Identification and validation of extracellular vesicle reference genes for the normalization of RT-qPCR data.
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Pinheiro C, Guilbert N, Lippens L, Roux Q, Boiy R, Fischer S, Van Dorpe S, De Craene B, Berx G, Boterberg T, Sys G, Denys H, Miinalainen I, Mestdagh P, Vandesompele J, De Wever O, and Hendrix A
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- Humans, RNA metabolism, Cell Line, Cells, Cultured, snRNP Core Proteins metabolism, Reverse Transcription, Extracellular Vesicles genetics, Extracellular Vesicles metabolism
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Extracellular vesicles (EVs) contain a plethora of biomolecules, including nucleic acids, with diverse diagnostic and therapeutic application potential. Although reverse transcription-quantitative PCR (RT-qPCR) is the most widely applied laboratory technique to evaluate gene expression, its applicability in EV research is challenged by the lack of universal and stably present reference genes (RGs). In this study, we identify, validate and establish SNRPG, OST4, TOMM7 and NOP10 as RGs for the normalization of EV-associated genes by RT-qPCR. We show the stable presence of SNRPG, OST4, TOMM7 and NOP10 in multiple cell lines and their secreted EVs (n = 12) under different (patho)physiological conditions as well as in human-derived biofluids (n = 3). Enzymatic treatments confirm the presence of SNRPG, OST4, TOMM7 and NOP10 inside EVs. In addition, the four EV-associated RGs are stably detected in a size-range of EV subpopulations. RefFinder analysis reveals that SNRPG, OST4, TOMM7 and NOP10 are more stable compared to RGs established specifically for cultured cells or tissues such as HMBS, YWHAZ, SDHA and GAPDH. In summary, we present four universal and stably present EV-associated RGs to enable normalization and thus steer the implementation of RT-qPCR for the analysis of EV-associated RNA cargo for research or clinical applications., (© 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.) more...
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- 2024
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46. Generation of post-surgical minimal residual disease models to investigate metastasis in soft tissue sarcoma patient-derived orthotopic xenografts.
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Fischer S, Creytens D, Gijsels S, Descamps B, Lapeire L, Hendrix A, Sys G, and De Wever O
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- Humans, Neoplasm, Residual, Heterografts, Magnetic Resonance Imaging, Sarcoma diagnostic imaging, Sarcoma surgery, Sarcoma pathology, Soft Tissue Neoplasms diagnostic imaging, Soft Tissue Neoplasms surgery, Soft Tissue Neoplasms pathology
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Despite optimal multimodal treatment including surgical resection, 50%-80% of high-grade soft tissue sarcoma (STS) patients metastasize. Here, we present a protocol for the generation and use of post-surgical minimal residual disease models to investigate metastatic relapse in STS patient-derived xenografts. We describe steps for orthotopic engraftment of high-grade STS patient-derived tumor tissue. We then detail procedures for primary tumor resection with broad, negative resection margins and follow-up until metastases using MRI. For complete details on the use and execution of this protocol, please refer to Fischer et al. (2023).
1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) more...- Published
- 2024
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47. Glioblastoma-Associated Mesenchymal Stem/Stromal Cells and Cancer-Associated Fibroblasts: Partners in Crime?
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Lootens T, Roman BI, Stevens CV, De Wever O, and Raedt R
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- Humans, Signal Transduction, Crime, Tumor Microenvironment, Fibroblasts pathology, Glioblastoma metabolism, Cancer-Associated Fibroblasts, Mesenchymal Stem Cells metabolism
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Tumor-associated mesenchymal stem/stromal cells (TA-MSCs) have been recognized as attractive therapeutic targets in several cancer types, due to their ability to enhance tumor growth and angiogenesis and their contribution to an immunosuppressive tumor microenvironment (TME). In glioblastoma (GB), mesenchymal stem cells (MSCs) seem to be recruited to the tumor site, where they differentiate into glioblastoma-associated mesenchymal stem/stromal cells (GA-MSCs) under the influence of tumor cells and the TME. GA-MSCs are reported to exert important protumoral functions, such as promoting tumor growth and invasion, increasing angiogenesis, stimulating glioblastoma stem cell (GSC) proliferation and stemness, mediating resistance to therapy and contributing to an immunosuppressive TME. Moreover, they could act as precursor cells for cancer-associated fibroblasts (CAFs), which have recently been identified in GB. In this review, we provide an overview of the different functions exerted by GA-MSCs and CAFs and the current knowledge on the relationship between these cell types. Increasing our understanding of the interactions and signaling pathways in relevant models might contribute to future regimens targeting GA-MSCs and GB-associated CAFs to inhibit tumor growth and render the TME less immunosuppressive. more...
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- 2024
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48. Histologic tumor type as a determinant of survival in hormone receptor-positive, HER2-negative, pT1-3 invasive ductal and lobular breast cancer.
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Göker M, Denys H, Hendrix A, De Wever O, Van de Vijver K, and Braems G
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- Humans, Female, Treatment Outcome, Proportional Hazards Models, Prognosis, Retrospective Studies, Carcinoma, Lobular pathology, Breast Neoplasms pathology, Carcinoma, Ductal, Breast pathology
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Purpose: The aim of the study was to compare the difference in survival between invasive ductal (IDC) and lobular carcinoma (ILC)., Methods: Data of patients (n = 1843) with a hormone receptor-positive, HER2-negative, pT1-3 IDC or ILC cancer without distant metastasis, treated at the Ghent University Hospital over the time period 2001-2015, were analyzed., Results: ILC represented 13.9% of the tumors, had a higher percentage of pT3 and pN3 stages than IDC, lymphovascular space invasion (LVSI) was less present and Ki-67 was mostly low. 73.9% of ILCs were grade 2, whereas IDC had more grade 1 and grade 3 tumors. Kaplan-Meier curves and log-rank testing showed a significant worse DFS for ILC with pN ≥ 1 than for their IDC counterpart. In a multivariable Cox regression analysis the histologic tumor type, ductal or lobular, was a determinant of DFS over 120 months (IDC as reference; hazard ratio for ILC 1.77, 95% CI 1.08-2.90) just as the ER Allred score (hazard ratio 0.84, 95% CI 0.78-0.91), LVSI (hazard ratio 1.75, 95% CI 1.12-2.74) and pN3 (hazard ratio 2.29, 95% CI 1.03-5.09). Determinants of OS over ten years were age (hazard ratio 1.05, 95% CI 1.02-1.07), LVSI (hazard ratio 3.62, 95% CI 1.92-6.82) and the ER Allred score (hazard ratio 0.80, 95% CI 0.73-0.89)., Conclusion: The histologic tumor type, ductal or lobular, determines DFS in hormone receptor-positive, HER2-negative, pT1-3 breast cancer besides the ER Allred score, LVSI and pN3., (© 2023. The Author(s).) more...
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- 2023
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49. A preclinical platform for assessing long-term drug efficacy exploiting mechanically tunable scaffolds colonized by a three-dimensional tumor microenvironment.
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De Vlieghere E, Van de Vijver K, Blondeel E, Carpentier N, Ghobeira R, Pauwels J, Riemann S, Minsart M, Fieuws C, Mestach J, Baeyens A, De Geyter N, Debbaut C, Denys H, Descamps B, Claes K, Vral A, Van Dorpe J, Gevaert K, De Geest BG, Ceelen W, Van Vlierberghe S, and De Wever O more...
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Background: Long-term drug evaluation heavily relies upon rodent models. Drug discovery methods to reduce animal models in oncology may include three-dimensional (3D) cellular systems that take into account tumor microenvironment (TME) cell types and biomechanical properties., Methods: In this study we reconstructed a 3D tumor using an elastic polymer (acrylate-endcapped urethane-based poly(ethylene glycol) (AUPPEG)) with clinical relevant stiffness. Single cell suspensions from low-grade serous ovarian cancer (LGSOC) patient-derived early passage cultures of cancer cells and cancer-associated fibroblasts (CAF) embedded in a collagen gel were introduced to the AUPPEG scaffold. After self-organization in to a 3D tumor, this model was evaluated by a long-term (> 40 days) exposure to a drug combination of MEK and HSP90 inhibitors. The drug-response results from this long-term in vitro model are compared with drug responses in an orthotopic LGSOC xenograft mouse model., Results: The in vitro 3D scaffold LGSOC model mimics the growth ratio and spatial organization of the LGSOC. The AUPPEG scaffold approach allows to test new targeted treatments and monitor long-term drug responses. The results correlate with those of the orthotopic LGSOC xenograft mouse model., Conclusions: The mechanically-tunable scaffolds colonized by a three-dimensional LGSOC allow long-term drug evaluation and can be considered as a valid alternative to reduce, replace and refine animal models in drug discovery., (© 2023. The Korean Society for Biomaterials.) more...
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- 2023
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50. Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis.
- Author
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González-Muñoz T, Di Giannatale A, García-Silva S, Santos V, Sánchez-Redondo S, Savini C, Graña-Castro O, Blanco-Aparicio C, Fischer S, De Wever O, Creus-Bachiller E, Ortega-Bertran S, Pisapia DJ, Rodríguez-Peralto JL, Fernández-Rodríguez J, Pérez-Portabella CR, Alaggio R, Benassi MS, Pazzaglia L, Scotlandi K, Ratner N, Yohay K, Theuer CP, and Peinado H more...
- Subjects
- Humans, Biomarkers, Cell Line, Tumor, Endoglin genetics, Mitogen-Activated Protein Kinase Kinases metabolism, Signal Transduction, Nerve Sheath Neoplasms drug therapy, Nerve Sheath Neoplasms genetics, Nerve Sheath Neoplasms metabolism, Neurofibrosarcoma
- Abstract
Purpose: Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive soft-tissue sarcomas that lack effective treatments, underscoring the urgent need to uncover novel mediators of MPNST pathogenesis that may serve as potential therapeutic targets. Tumor angiogenesis is considered a critical event in MPNST transformation and progression. Here, we have investigated whether endoglin (ENG), a TGFβ coreceptor with a crucial role in angiogenesis, could be a novel therapeutic target in MPNSTs., Experimental Design: ENG expression was evaluated in human peripheral nerve sheath tumor tissues and plasma samples. Effects of tumor cell-specific ENG expression on gene expression, signaling pathway activation and in vivo MPNST growth and metastasis, were investigated. The efficacy of ENG targeting in monotherapy or in combination with MEK inhibition was analyzed in xenograft models., Results: ENG expression was found to be upregulated in both human MPNST tumor tissues and plasma-circulating small extracellular vesicles. We demonstrated that ENG modulates Smad1/5 and MAPK/ERK pathway activation and pro-angiogenic and pro-metastatic gene expression in MPNST cells and plays an active role in tumor growth and metastasis in vivo. Targeting with ENG-neutralizing antibodies (TRC105/M1043) decreased MPNST growth and metastasis in xenograft models by reducing tumor cell proliferation and angiogenesis. Moreover, combination of anti-ENG therapy with MEK inhibition effectively reduced tumor cell growth and angiogenesis., Conclusions: Our data unveil a tumor-promoting function of ENG in MPNSTs and support the use of this protein as a novel biomarker and a promising therapeutic target for this disease., (©2023 American Association for Cancer Research.) more...
- Published
- 2023
- Full Text
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