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1. Correlation Between Endoglin and Malignant Phenotype in Human Melanoma Cells: Analysis of hsa-mir-214 and hsa-mir-370 in Cells and Their Extracellular Vesicles

Author

Ruiz-Llorente, Lidia, Ruiz-Rodríguez, María Jesús, Savini, Claudia, González-Muñoz, Teresa, Riveiro-Falkenbach, Erica, Rodríguez-Peralto, José L., Peinado, Héctor, Bernabeu, Carmelo, Crusio, Wim E., Series Editor, Dong, Haidong, Series Editor, Radeke, Heinfried H., Series Editor, Rezaei, Nima, Series Editor, Steinlein, Ortrud, Series Editor, Xiao, Junjie, Series Editor, Simon, Felipe, editor, and Bernabeu, Carmelo, editor

Published
2023
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3. Supplementary Data 3 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

Author

González-Muñoz, Teresa, primary, Di Giannatale, Angela, primary, García-Silva, Susana, primary, Santos, Vanesa, primary, Sánchez-Redondo, Sara, primary, Savini, Claudia, primary, Graña-Castro, Osvaldo, primary, Blanco-Aparicio, Carmen, primary, Fischer, Suzanne, primary, De Wever, Olivier, primary, Creus-Bachiller, Edgar, primary, Ortega-Bertran, Sara, primary, Pisapia, David J., primary, Rodríguez-Peralto, Jose L., primary, Fernández-Rodríguez, Juana, primary, Pérez-Portabella, Cleofé Romagosa, primary, Alaggio, Rita, primary, Benassi, Maria Serena, primary, Pazzaglia, Laura, primary, Scotlandi, Katia, primary, Ratner, Nancy, primary, Yohay, Kaleb, primary, Theuer, Charles P., primary, and Peinado, Héctor, primary

Published
2023
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4. Supplementary Data 2 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

Author

González-Muñoz, Teresa, primary, Di Giannatale, Angela, primary, García-Silva, Susana, primary, Santos, Vanesa, primary, Sánchez-Redondo, Sara, primary, Savini, Claudia, primary, Graña-Castro, Osvaldo, primary, Blanco-Aparicio, Carmen, primary, Fischer, Suzanne, primary, De Wever, Olivier, primary, Creus-Bachiller, Edgar, primary, Ortega-Bertran, Sara, primary, Pisapia, David J., primary, Rodríguez-Peralto, Jose L., primary, Fernández-Rodríguez, Juana, primary, Pérez-Portabella, Cleofé Romagosa, primary, Alaggio, Rita, primary, Benassi, Maria Serena, primary, Pazzaglia, Laura, primary, Scotlandi, Katia, primary, Ratner, Nancy, primary, Yohay, Kaleb, primary, Theuer, Charles P., primary, and Peinado, Héctor, primary

Published
2023
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5. Suppl. Figure 6 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

Author

González-Muñoz, Teresa, primary, Di Giannatale, Angela, primary, García-Silva, Susana, primary, Santos, Vanesa, primary, Sánchez-Redondo, Sara, primary, Savini, Claudia, primary, Graña-Castro, Osvaldo, primary, Blanco-Aparicio, Carmen, primary, Fischer, Suzanne, primary, De Wever, Olivier, primary, Creus-Bachiller, Edgar, primary, Ortega-Bertran, Sara, primary, Pisapia, David J., primary, Rodríguez-Peralto, Jose L., primary, Fernández-Rodríguez, Juana, primary, Pérez-Portabella, Cleofé Romagosa, primary, Alaggio, Rita, primary, Benassi, Maria Serena, primary, Pazzaglia, Laura, primary, Scotlandi, Katia, primary, Ratner, Nancy, primary, Yohay, Kaleb, primary, Theuer, Charles P., primary, and Peinado, Héctor, primary

Published
2023
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6. Suppl. Figure 5 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

Author

González-Muñoz, Teresa, primary, Di Giannatale, Angela, primary, García-Silva, Susana, primary, Santos, Vanesa, primary, Sánchez-Redondo, Sara, primary, Savini, Claudia, primary, Graña-Castro, Osvaldo, primary, Blanco-Aparicio, Carmen, primary, Fischer, Suzanne, primary, De Wever, Olivier, primary, Creus-Bachiller, Edgar, primary, Ortega-Bertran, Sara, primary, Pisapia, David J., primary, Rodríguez-Peralto, Jose L., primary, Fernández-Rodríguez, Juana, primary, Pérez-Portabella, Cleofé Romagosa, primary, Alaggio, Rita, primary, Benassi, Maria Serena, primary, Pazzaglia, Laura, primary, Scotlandi, Katia, primary, Ratner, Nancy, primary, Yohay, Kaleb, primary, Theuer, Charles P., primary, and Peinado, Héctor, primary

Published
2023
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7. Suppl. Figure 1 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

Author

González-Muñoz, Teresa, primary, Di Giannatale, Angela, primary, García-Silva, Susana, primary, Santos, Vanesa, primary, Sánchez-Redondo, Sara, primary, Savini, Claudia, primary, Graña-Castro, Osvaldo, primary, Blanco-Aparicio, Carmen, primary, Fischer, Suzanne, primary, De Wever, Olivier, primary, Creus-Bachiller, Edgar, primary, Ortega-Bertran, Sara, primary, Pisapia, David J., primary, Rodríguez-Peralto, Jose L., primary, Fernández-Rodríguez, Juana, primary, Pérez-Portabella, Cleofé Romagosa, primary, Alaggio, Rita, primary, Benassi, Maria Serena, primary, Pazzaglia, Laura, primary, Scotlandi, Katia, primary, Ratner, Nancy, primary, Yohay, Kaleb, primary, Theuer, Charles P., primary, and Peinado, Héctor, primary

Published
2023
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8. Supplementary Data 1 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

Author

González-Muñoz, Teresa, primary, Di Giannatale, Angela, primary, García-Silva, Susana, primary, Santos, Vanesa, primary, Sánchez-Redondo, Sara, primary, Savini, Claudia, primary, Graña-Castro, Osvaldo, primary, Blanco-Aparicio, Carmen, primary, Fischer, Suzanne, primary, De Wever, Olivier, primary, Creus-Bachiller, Edgar, primary, Ortega-Bertran, Sara, primary, Pisapia, David J., primary, Rodríguez-Peralto, Jose L., primary, Fernández-Rodríguez, Juana, primary, Pérez-Portabella, Cleofé Romagosa, primary, Alaggio, Rita, primary, Benassi, Maria Serena, primary, Pazzaglia, Laura, primary, Scotlandi, Katia, primary, Ratner, Nancy, primary, Yohay, Kaleb, primary, Theuer, Charles P., primary, and Peinado, Héctor, primary

Published
2023
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9. Suppl. Figure 4 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

Author

González-Muñoz, Teresa, primary, Di Giannatale, Angela, primary, García-Silva, Susana, primary, Santos, Vanesa, primary, Sánchez-Redondo, Sara, primary, Savini, Claudia, primary, Graña-Castro, Osvaldo, primary, Blanco-Aparicio, Carmen, primary, Fischer, Suzanne, primary, De Wever, Olivier, primary, Creus-Bachiller, Edgar, primary, Ortega-Bertran, Sara, primary, Pisapia, David J., primary, Rodríguez-Peralto, Jose L., primary, Fernández-Rodríguez, Juana, primary, Pérez-Portabella, Cleofé Romagosa, primary, Alaggio, Rita, primary, Benassi, Maria Serena, primary, Pazzaglia, Laura, primary, Scotlandi, Katia, primary, Ratner, Nancy, primary, Yohay, Kaleb, primary, Theuer, Charles P., primary, and Peinado, Héctor, primary

Published
2023
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10. Suppl. Figure 3 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

Author

González-Muñoz, Teresa, primary, Di Giannatale, Angela, primary, García-Silva, Susana, primary, Santos, Vanesa, primary, Sánchez-Redondo, Sara, primary, Savini, Claudia, primary, Graña-Castro, Osvaldo, primary, Blanco-Aparicio, Carmen, primary, Fischer, Suzanne, primary, De Wever, Olivier, primary, Creus-Bachiller, Edgar, primary, Ortega-Bertran, Sara, primary, Pisapia, David J., primary, Rodríguez-Peralto, Jose L., primary, Fernández-Rodríguez, Juana, primary, Pérez-Portabella, Cleofé Romagosa, primary, Alaggio, Rita, primary, Benassi, Maria Serena, primary, Pazzaglia, Laura, primary, Scotlandi, Katia, primary, Ratner, Nancy, primary, Yohay, Kaleb, primary, Theuer, Charles P., primary, and Peinado, Héctor, primary

Published
2023
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11. Data from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

Author

González-Muñoz, Teresa, primary, Di Giannatale, Angela, primary, García-Silva, Susana, primary, Santos, Vanesa, primary, Sánchez-Redondo, Sara, primary, Savini, Claudia, primary, Graña-Castro, Osvaldo, primary, Blanco-Aparicio, Carmen, primary, Fischer, Suzanne, primary, De Wever, Olivier, primary, Creus-Bachiller, Edgar, primary, Ortega-Bertran, Sara, primary, Pisapia, David J., primary, Rodríguez-Peralto, Jose L., primary, Fernández-Rodríguez, Juana, primary, Pérez-Portabella, Cleofé Romagosa, primary, Alaggio, Rita, primary, Benassi, Maria Serena, primary, Pazzaglia, Laura, primary, Scotlandi, Katia, primary, Ratner, Nancy, primary, Yohay, Kaleb, primary, Theuer, Charles P., primary, and Peinado, Héctor, primary

Published
2023
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12. Suppl. Figure 2 from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

Author

González-Muñoz, Teresa, primary, Di Giannatale, Angela, primary, García-Silva, Susana, primary, Santos, Vanesa, primary, Sánchez-Redondo, Sara, primary, Savini, Claudia, primary, Graña-Castro, Osvaldo, primary, Blanco-Aparicio, Carmen, primary, Fischer, Suzanne, primary, De Wever, Olivier, primary, Creus-Bachiller, Edgar, primary, Ortega-Bertran, Sara, primary, Pisapia, David J., primary, Rodríguez-Peralto, Jose L., primary, Fernández-Rodríguez, Juana, primary, Pérez-Portabella, Cleofé Romagosa, primary, Alaggio, Rita, primary, Benassi, Maria Serena, primary, Pazzaglia, Laura, primary, Scotlandi, Katia, primary, Ratner, Nancy, primary, Yohay, Kaleb, primary, Theuer, Charles P., primary, and Peinado, Héctor, primary

Published
2023
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15. Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer

Author

Sansone, Pasquale, Savini, Claudia, Kurelac, Ivana, Chang, Qing, Amato, Laura Benedetta, Strillacci, Antonio, Stepanova, Anna, Iommarini, Luisa, Mastroleo, Chiara, Daly, Laura, Galkin, Alexander, Thakur, Basant Kumar, Soplop, Nadine, Uryu, Kunihiro, Hoshino, Ayuko, Norton, Larry, Bonafé, Massimiliano, Cricca, Monica, Gasparre, Giuseppe, Lyden, David, and Bromberg, Jacqueline

Published
2017

16. Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

Author

González-Muñoz, Teresa, primary, Di Giannatale, Angela, additional, García-Silva, Susana, additional, Santos, Vanesa, additional, Sánchez-Redondo, Sara, additional, Savini, Claudia, additional, Graña-Castro, Osvaldo, additional, Blanco-Aparicio, Carmen, additional, Fischer, Suzanne, additional, De Wever, Olivier, additional, Creus-Bachiller, Edgar, additional, Ortega-Bertran, Sara, additional, Pisapia, David J., additional, Rodríguez-Peralto, Jose L., additional, Fernández-Rodríguez, Juana, additional, Pérez-Portabella, Cleofé Romagosa, additional, Alaggio, Rita, additional, Benassi, Maria Serena, additional, Pazzaglia, Laura, additional, Scotlandi, Katia, additional, Ratner, Nancy, additional, Yohay, Kaleb, additional, Theuer, Charles P., additional, and Peinado, Héctor, additional

Published
2023
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17. Data from Evolution of Cancer Stem-like Cells in Endocrine-Resistant Metastatic Breast Cancers Is Mediated by Stromal Microvesicles

Author

Sansone, Pasquale, primary, Berishaj, Marjan, primary, Rajasekhar, Vinagolu K., primary, Ceccarelli, Claudio, primary, Chang, Qing, primary, Strillacci, Antonio, primary, Savini, Claudia, primary, Shapiro, Lauren, primary, Bowman, Robert L., primary, Mastroleo, Chiara, primary, De Carolis, Sabrina, primary, Daly, Laura, primary, Benito-Martin, Alberto, primary, Perna, Fabiana, primary, Fabbri, Nicola, primary, Healey, John H., primary, Spisni, Enzo, primary, Cricca, Monica, primary, Lyden, David, primary, Bonafé, Massimiliano, primary, and Bromberg, Jacqueline, primary

Published
2023
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18. Supplementary data from Evolution of Cancer Stem-like Cells in Endocrine-Resistant Metastatic Breast Cancers Is Mediated by Stromal Microvesicles

Author

Sansone, Pasquale, primary, Berishaj, Marjan, primary, Rajasekhar, Vinagolu K., primary, Ceccarelli, Claudio, primary, Chang, Qing, primary, Strillacci, Antonio, primary, Savini, Claudia, primary, Shapiro, Lauren, primary, Bowman, Robert L., primary, Mastroleo, Chiara, primary, De Carolis, Sabrina, primary, Daly, Laura, primary, Benito-Martin, Alberto, primary, Perna, Fabiana, primary, Fabbri, Nicola, primary, Healey, John H., primary, Spisni, Enzo, primary, Cricca, Monica, primary, Lyden, David, primary, Bonafé, Massimiliano, primary, and Bromberg, Jacqueline, primary

Published
2023
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19. Endoglin, a novel biomarker and therapeutical target to prevent malignant peripheral nerve sheath tumor growth and metastasis

Author

González-Muñoz, Teresa, primary, Di Giannatale, Angela, additional, García-Silva, Susana, additional, Santos, Vanesa, additional, Sánchez-Redondo, Sara, additional, Savini, Claudia, additional, Graña-Castro, Osvaldo, additional, Blanco-Aparicio, Carmen, additional, Pisapia, David J, additional, Rodríguez-Peralto, Jose L, additional, Romagosa Pérez-Portabella, Cleofé, additional, Alaggio, Rita, additional, Benassi, Maria Serena, additional, Pazzaglia, Laura, additional, Scotlandi, Katia, additional, Ratner, Nancy, additional, Yohay, Kaleb, additional, Theuer, Charles P., additional, and Peinado, Héctor, additional

Published
2022
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21. Adaptation of TECCU App Based on Patients´ Perceptions for the Telemonitoring of Inflammatory Bowel Disease: A Qualitative Study Using Focus Groups

Author

Del Hoyo, Javier, primary, Nos, Pilar, additional, Faubel, Raquel, additional, Bastida, Guillermo, additional, Muñoz, Diana, additional, Valero-Pérez, Elena, additional, Garrido-Marín, Alejandro, additional, Bella, Pablo, additional, Peña, Beatriz, additional, Savini, Claudia, additional, and Aguas, Mariam, additional

Published
2020
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22. HPV DNA Associates With Breast Cancer Malignancy and It Is Transferred to Breast Cancer Stromal Cells by Extracellular Vesicles

Author

De Carolis, Sabrina, primary, Storci, Gianluca, additional, Ceccarelli, Claudio, additional, Savini, Claudia, additional, Gallucci, Lara, additional, Sansone, Pasquale, additional, Santini, Donatella, additional, Seracchioli, Renato, additional, Taffurelli, Mario, additional, Fabbri, Francesco, additional, Romani, Fabrizio, additional, Compagnone, Gaetano, additional, Giuliani, Cristina, additional, Garagnani, Paolo, additional, Bonafè, Massimiliano, additional, and Cricca, Monica, additional

Published
2019
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25. Evolution of Cancer Stem-like Cells in Endocrine-Resistant Metastatic Breast Cancers Is Mediated by Stromal Microvesicles

Author

Sansone, Pasquale, primary, Berishaj, Marjan, additional, Rajasekhar, Vinagolu K., additional, Ceccarelli, Claudio, additional, Chang, Qing, additional, Strillacci, Antonio, additional, Savini, Claudia, additional, Shapiro, Lauren, additional, Bowman, Robert L., additional, Mastroleo, Chiara, additional, De Carolis, Sabrina, additional, Daly, Laura, additional, Benito-Martin, Alberto, additional, Perna, Fabiana, additional, Fabbri, Nicola, additional, Healey, John H., additional, Spisni, Enzo, additional, Cricca, Monica, additional, Lyden, David, additional, Bonafé, Massimiliano, additional, and Bromberg, Jacqueline, additional

Published
2017
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26. Papillomavirus associated malignancies in dogs and cats

Author

SAVINI, FEDERICA, SABATTINI, SILVIA, GALLINA, LAURA, SAVINI, CLAUDIA, CRICCA, MONICA, BONAFE', MASSIMILIANO, SCAGLIARINI, ALESSANDRA, BASSI, PATRIZIA, BETTINI, GIULIANO, De Oliveira, J. G., Savini, F., Sabattini, S., Gallina, L., Savini, C., Cricca, M., Bonafè, M., De Oliveira, J.G., Scagliarini, A., Bassi, P., and Bettini, G.

Subjects
Papillomavirus, cancerogenesis, animal models, dog, cat
Abstract

Papillomaviruses (PVs) infect many species of mammals and play an important role in human cancer development, and have been isolated from a number of human and animal malignancies. Here we present the preliminary findings of an investigation that is being carried out to deepen the association between papillomavirus and cancer in dogs and cats. Archive samples of 55 canine and 15 feline cutaneous and mucosal squamous cell carcinomas (SCC), and 10 canine and feline mammary carcinomas were tested with PCR to assess PV infection and immunohistochemically for p16 expression that is linked to the oncogenic activity of PV. Squamous cell carcinoma is a common malignancy in animal species, including cats, dogs, horses and sheep, which shares strict clinical and pathological similarities with human head and neck cancer. Our data strengthen the association between PV and feline SCC, as suggested by the identification of FdPV2 sequence in two cats affected by SCC in the ear pinna (6770) and neck (224/06), the latter showing strong p16 labelling. Furthermore, a feline SCC in the lip (855/02) carried PV DNA with L1 sequence 100% identical to HPV FA 16.3, supporting a possible relation between HPV types and feline SCC. In dogs, the role of PVs is well acknowledged in cutaneous and oral papillomatosis, but still controversial in SCC. In our samples, we identified PV DNA in a canine SCC (998) of the neck, whose nucleotide sequence showed 94% identity with CPV-1. As for mammary carcinomas, in two canine cases we identified a PV L1 sequence, showing 94% identity with human papillomavirus type 9 (32410, luminal B type) and 92 (40897, basal type). Our results confirm the already reported hypothetical transmission of papillomaviruses between humans and cats, and suggest that transmission may be possible also in dogs. The association between canine mammary cancer and PVs needs further confirmation. Indeed, the dog represents an increasingly powerful spontaneous animal model for the translational study of human breast cancer, in which several types of PVs seem to play a role. Further researches will be also needed to elucidate if CPV-1 may be the responsible or just an innocent by-stander in canine SCC development.

Published
2015

27. Transfer of Viral and Mitochondrial Nucleic Acids through Microvesicles: a Possible Mechanism of Genetic Intra-Tumor Heterogeneity in Breast Cancer

Author

Cricca, Monica, Savini, Claudia <1987>, Cricca, Monica, and Savini, Claudia <1987>

Abstract

Microvesicles (MVs) are small extracellular vesicles divided in exosomes (40-100nm), shedding microvesicles (100nm–1µm), and apoptotic bodies (1-5µm). MVs contain bioactive molecules, nucleic acids and proteins and are physiologically secreted by cells in order to guarantee cell-to-cell communication. The presence of viral miRNA in exosomes and viral DNA in apoptotic bodies was demonstrated. Viral DNA sequences like EBV and HPV have been identified in numerous cancers tissues, like in breast cancer, in the absence of a primary infection. Two meta-analyses studies analyzed the presence of HPV and EBV sequences in breast cancer tissues worldwide, and identified the viral nucleic acids in the 23% and 29% of the samples, respectively. However, the mechanisms of viral DNA acquisition in this cancer have not been investigated. This paper demonstrates the presence of viral nucleic acids in MVs coming from cell line models of onco-viral dependent transformation, including cervical carcinoma (HPV) and lymphoma (EBV), and their transfer through MVs to viral negative epithelial cells and fibroblasts. The presence and transfer of murine mitochondrial DNA in MVs coming from murine cancer-associated fibroblasts is also demonstrated, as well as its transfer to human recipient cells. This study also shows the presence of viral HPV16/18/31 DNA in the circulating MVs from two different cohorts: one of newly diagnosed breast cancer patients, collected in Bologna, Italy, and the other one of patients affected by hormonal therapy-resistant breast cancer, collected in New York, USA. The presence of DNaseI-resistant DNA in the RNA fraction prompted us to study the physical-chemical status of the viral DNA sequences packaged in the MVs coming from viral positive cell lines; the DNA is found in the form of DNA:RNA hybrids (R-loops), which are known to be more stable structures, mostly synthesized in hypoxic conditions.

Published
2016

29. Evolution of Cancer Stem-like Cells in Endocrine-Resistant Metastatic Breast Cancers Is Mediated by Stromal Microvesicles

Author

Alberto Benito-Martin, Antonio Strillacci, David Lyden, Claudia Savini, Pasquale Sansone, Sabrina De Carolis, John H. Healey, Enzo Spisni, Robert L. Bowman, Qing Chang, Vinagolu K. Rajasekhar, Chiara Mastroleo, Marjan Berishaj, Fabiana Perna, Massimiliano Bonafè, Laura Daly, Nicola Fabbri, Monica Cricca, Claudio Ceccarelli, Jacqueline Bromberg, Lauren Q. Shapiro, Sansone, Pasquale, Berishaj, Marjan, Rajasekhar, Vinagolu K, Ceccarelli, Claudio, Chang, Qing, Strillacci, Antonio, Savini, Claudia, Shapiro, Lauren, Bowman, Robert, Mastroleo, Chiara, De Carolis, Sabrina, Daly, Laura, Benito-Martin, Alberto, Perna, Fabiana, Fabbri, Nicola, Healey, John H, Spisni, Enzo, Cricca, Monica, Lyden, David, Bonafé, Massimiliano, and Bromberg, Jacqueline

Subjects
STAT3 Transcription Factor, 0301 basic medicine, Cancer Research, Pathology, medicine.medical_specialty, Neoplasms, Hormone-Dependent, Stromal cell, Antineoplastic Agents, Hormonal, Breast Neoplasms, Mice, SCID, Biology, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Cancer-Associated Fibroblasts, Cell-Derived Microparticles, Mice, Inbred NOD, Cancer stem cell, medicine, Animals, Humans, breast cancer, stromal microvesicles, endocrine resistant metastatic breast cancer, Fulvestrant, Estradiol, Interleukin-6, Cancer, medicine.disease, Microvesicles, MicroRNAs, 030104 developmental biology, Oncology, Drug Resistance, Neoplasm, Case-Control Studies, 030220 oncology & carcinogenesis, Cancer cell, MCF-7 Cells, Neoplastic Stem Cells, Cancer research, Heterografts, Hormonal therapy, Female, Stromal Cells, Stem cell, HeLa Cells
Abstract

The hypothesis that microvesicle-mediated miRNA transfer converts noncancer stem cells into cancer stem cells (CSC) leading to therapy resistance remains poorly investigated. Here we provide direct evidence supporting this hypothesis, by demonstrating how microvesicles derived from cancer-associated fibroblasts (CAF) transfer miR-221 to promote hormonal therapy resistance (HTR) in models of luminal breast cancer. We determined that CAF-derived microvesicles horizontally transferred miR-221 to tumor cells and, in combination with hormone therapy, activated an ERlo/Notchhi feed-forward loop responsible for the generation of CD133hi CSCs. Importantly, microvesicles from patients with HTR metastatic disease expressed high levels of miR-221. We further determined that the IL6–pStat3 pathway promoted the biogenesis of onco-miR-221hi CAF microvesicles and established stromal CSC niches in experimental and patient-derived breast cancer models. Coinjection of patient-derived CAFs from bone metastases led to de novo HTR tumors, which was reversed with IL6R blockade. Finally, we generated patient-derived xenograft (PDX) models from patient-derived HTR bone metastases and analyzed tumor cells, stroma, and microvesicles. Murine and human CAFs were enriched in HTR tumors expressing high levels of CD133hi cells. Depletion of murine CAFs from PDX restored sensitivity to HT, with a concurrent reduction of CD133hi CSCs. Conversely, in models of CD133neg, HT-sensitive cancer cells, both murine and human CAFs promoted de novo HT resistance via the generation of CD133hi CSCs that expressed low levels of estrogen receptor alpha. Overall, our results illuminate how microvesicle-mediated horizontal transfer of genetic material from host stromal cells to cancer cells triggers the evolution of therapy-resistant metastases, with potentially broad implications for their control. Cancer Res; 77(8); 1927–41. ©2017 AACR.

Published
2017

30. Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer

Author

Claudia Savini, Laura Benedetta Amato, Basant Kumar Thakur, Jacqueline Bromberg, Giuseppe Gasparre, Chiara Mastroleo, Monica Cricca, Ivana Kurelac, Qing Chang, Massimiliano Bonafè, Kunihiro Uryu, Alexander Galkin, Anna Stepanova, Pasquale Sansone, Larry Norton, Nadine Soplop, David Lyden, Luisa Iommarini, Ayuko Hoshino, Laura Daly, Antonio Strillacci, Sansone, Pasquale, Savini, Claudia, Kurelac, Ivana, Chang, Qing, Amato, LAURA BENEDETTA, Strillacci, Antonio, Stepanova, Anna, Iommarini, Luisa, Mastroleo, Chiara, Daly, Laura, Galkin, Alexander, Thakur, Basant Kumar, Soplop, Nadine, Uryu, Kunihiro, Hoshinob, Ayuko, Norton, Larry, Bonafe', Massimiliano, Cricca, Monica, Gasparre, Giuseppe, Lyden, David, and Bromberg, Jacqueline

Subjects
0301 basic medicine, Mitochondrial DNA, exosomes, mitochondrial DNA, cancer stem cells, hormonal therapy, metastasis, Gene Transfer, Horizontal, Medizin, Breast Neoplasms, Biology, Exosomes, DNA, Mitochondrial, Corrections, Oxidative Phosphorylation, Metastasis, 03 medical and health sciences, Breast cancer, Cancer stem cell, Cell Line, Tumor, medicine, Humans, Multidisciplinary, Cancer, NADH Dehydrogenase, Fibroblasts, medicine.disease, Phenotype, Xenograft Model Antitumor Assays, Microvesicles, 3. Good health, 030104 developmental biology, Receptors, Estrogen, Drug Resistance, Neoplasm, Immunology, Genome, Mitochondrial, Cancer research, MCF-7 Cells, Hormonal therapy, Female
Abstract

The horizontal transfer of mtDNA and its role in mediating resistance to therapy and an exit from dormancy have never been investigated. Here we identified the full mitochondrial genome in circulating extracellular vesicles (EVs) from patients with hormonal therapy-resistant (HTR) metastatic breast cancer. We generated xenograft models of HTR metastatic disease characterized by EVs in the peripheral circulation containing mtDNA. Moreover, these human HTR cells had acquired host-derived (murine) mtDNA promoting estrogen receptor-independent oxidative phosphorylation (OXPHOS). Functional studies identified cancer-associated fibroblast (CAF)-derived EVs (from patients and xenograft models) laden with whole genomic mtDNA as a mediator of this phenotype. Specifically, the treatment of hormone therapy (HT)-naive cells or HT-treated metabolically dormant populations with CAF-derived mtDNAhi EVs promoted an escape from metabolic quiescence and HTR disease both in vitro and in vivo. Moreover, this phenotype was associated with the acquisition of EV mtDNA, especially in cancer stem-like cells, expression of EV mtRNA, and restoration of OXPHOS. In summary, we have demonstrated that the horizontal transfer of mtDNA from EVs acts as an oncogenic signal promoting an exit from dormancy of therapy-induced cancer stem-like cells and leading to endocrine therapy resistance in OXPHOS-dependent breast cancer.

Published
2017

31. High-throughput genotyping of high-risk Human Papillomavirus by MALDI-TOF Mass Spectrometry-based method

Author

Monica, Cricca, Elena, Marasco, Federica, Alessandrini, Chiara, Fazio, Anna, Prossomariti, Claudia, Savini, Simona, Venturoli, Pasquale, Chieco, Sabrina, De Carolis, Massimiliano, Bonafè, Maria Carla, Re, Paolo, Garagnani, Vilma, Mantovani, Monica, Cricca, Marasco, Elena, Federica, Alessandrini, Chiara, Fazio, Prossomariti, Anna, Savini, Claudia, Venturoli, Simona, Chieco, Pasquale, De Carolis, Sabrina, Bonafè, Massimiliano, Re, Maria Carla, Garagnani, Paolo, and Mantovani, Vilma

Subjects
Genotyping, HPV, Inno-LiPA, Genotype, Papillomavirus Infections, virus diseases, High-throughput, High-Throughput Screening Assays, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Cervical cancer, Humans, MALDI-TOF MS, Female, Papillomaviridae
Abstract

A high-throughput matrix-assisted laser desorption ionisation-time of flight (MALDI-TOF) mass spectrometry (MS)-based method was here developed to genotype 16 high-risk human papillomavirus (HPV) types in cervical cytology specimens. This method was compared to a commercial kit, the Inno-LiPA HPV genotyping assay, which detects a broad spectrum of HPV types. HPV DNA was assessed by the two methods in a total of 325 cervical cytology specimens collected in PreservCyt® solution. The overall agreement was almost perfect (Cohen's k=0.86) in term of positive and negative cases. Indeed, HPV types 16, 35, 56 and 66 showed the highest agreement values (>0.80). The highest agreement values (K >0.80) were found for all 16 HPV types in single infections, but only for HPV 16, 35, 45 and 56 in multiple infections. In conclusion, the high-throughput MS-based method developed here is well-suited for broad spectrum HPV genotyping in large-scale epidemiological studies.

Published
2015

32. High-throughput genotyping of high-risk Human Papillomavirus by MALDI-TOF Mass Spectrometry-based method.

Author

Cricca M, Marasco E, Alessandrini F, Fazio C, Prossomariti A, Savini C, Venturoli S, Chieco P, De Carolis S, Bonafè M, Re MC, Garagnani P, and Mantovani V

Subjects
Female, Genotype, Humans, Papillomaviridae chemistry, Papillomaviridae classification, Papillomaviridae genetics, High-Throughput Screening Assays methods, Papillomaviridae isolation & purification, Papillomavirus Infections virology, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods
Abstract

A high-throughput matrix-assisted laser desorption ionisation-time of flight (MALDI-TOF) mass spectrometry (MS)-based method was here developed to genotype 16 high-risk human papillomavirus (HPV) types in cervical cytology specimens. This method was compared to a commercial kit, the Inno-LiPA HPV genotyping assay, which detects a broad spectrum of HPV types. HPV DNA was assessed by the two methods in a total of 325 cervical cytology specimens collected in PreservCyt® solution. The overall agreement was almost perfect (Cohen's k=0.86) in term of positive and negative cases. Indeed, HPV types 16, 35, 56 and 66 showed the highest agreement values (>0.80). The highest agreement values (K >0.80) were found for all 16 HPV types in single infections, but only for HPV 16, 35, 45 and 56 in multiple infections. In conclusion, the high-throughput MS-based method developed here is well-suited for broad spectrum HPV genotyping in large-scale epidemiological studies.

Published
2015

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