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21 results on '"Wyns, Sabine"'

1. Role of glutamine synthetase in angiogenesis beyond glutamine synthesis

Author

Eelen, Guy, Dubois, Charlotte, Cantelmo, Anna Rita, Goveia, Jermaine, Brüning, Ulrike, DeRan, Michael, Jarugumilli, Gopala, van Rijssel, Jos, Saladino, Giorgio, Comitani, Federico, Zecchin, Annalisa, Rocha, Susana, Chen, Rongyuan, Huang, Hongling, Vandekeere, Saar, Kalucka, Joanna, Lange, Christian, Morales-Rodriguez, Francisco, Cruys, Bert, Treps, Lucas, Ramer, Leanne, Vinckier, Stefan, Brepoels, Katleen, Wyns, Sabine, Souffreau, Joris, Schoonjans, Luc, Lamers, Wouter H., Wu, Yi, Haustraete, Jurgen, Hofkens, Johan, Liekens, Sandra, Cubbon, Richard, Ghesquière, Bart, Dewerchin, Mieke, Gervasio, Francesco L., Li, Xuri, van Buul, Jaap D., Wu, Xu, and Carmeliet, Peter

Published
2018
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2. Role of glutamine and interlinked asparagine metabolism in vessel formation

Author

Huang, Hongling, Vandekeere, Saar, Kalucka, Joanna, Bierhansl, Laura, Zecchin, Annalisa, Brüning, Ulrike, Visnagri, Asjad, Yuldasheva, Nadira, Goveia, Jermaine, Cruys, Bert, Brepoels, Katleen, Wyns, Sabine, Rayport, Stephen, Ghesquière, Bart, Vinckier, Stefan, Schoonjans, Luc, Cubbon, Richard, Dewerchin, Mieke, Eelen, Guy, and Carmeliet, Peter

Published
2017
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3. The role of fatty acid β-oxidation in lymphangiogenesis

Author

Wong, Brian W., Wang, Xingwu, Zecchin, Annalisa, Thienpont, Bernard, Cornelissen, Ivo, Kalucka, Joanna, García-Caballero, Melissa, Missiaen, Rindert, Huang, Hongling, Brüning, Ulrike, Blacher, Silvia, Vinckier, Stefan, Goveia, Jermaine, Knobloch, Marlen, Zhao, Hui, Dierkes, Cathrin, Shi, Chenyan, Hägerling, René, Moral-Dardé, Veronica, Wyns, Sabine, Lippens, Martin, Jessberger, Sebastian, Fendt, Sarah-Maria, Luttun, Aernout, Noel, Agnès, Kiefer, Friedemann, Ghesquière, Bart, Moons, Lieve, Schoonjans, Luc, Dewerchin, Mieke, Eelen, Guy, Lambrechts, Diether, and Carmeliet, Peter

Published
2017
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4. HRG Inhibits Tumor Growth and Metastasis by Inducing Macrophage Polarization and Vessel Normalization through Downregulation of PlGF

Author

Rolny, Charlotte, Mazzone, Massimiliano, Tugues, Sònia, Laoui, Damya, Johansson, Irja, Coulon, Cathy, Squadrito, Mario Leonardo, Segura, Inmaculada, Li, Xiujuan, Knevels, Ellen, Costa, Sandra, Vinckier, Stefan, Dresselaer, Tom, Åkerud, Peter, De Mol, Maria, Salomäki, Henriikka, Phillipson, Mia, Wyns, Sabine, Larsson, Erik, Buysschaert, Ian, Botling, Johan, Himmelreich, Uwe, Van Ginderachter, Jo A., De Palma, Michele, Dewerchin, Mieke, Claesson-Welsh, Lena, and Carmeliet, Peter

Published
2011
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5. The role of fatty acid -oxidation in lymphangiogenesis

Author

Wong, Brian W., Wang, Xingwu, Zecchin, Annalisa, Thienpont, Bernard, Cornelissen, Ivo, Kalucka, Joanna, Garca-Caballero, Melissa, Missiaen, Rindert, Huang, Hongling, Brning, Ulrike, Blacher, Silvia, Vinckier, Stefan, Goveia, Jermaine, Knobloch, Marlen, Zhao, Hui, Dierkes, Cathrin, Shi, Chenyan, Hgerling, Ren, Moral-Dard, Veronica, Wyns, Sabine, Lippens, Martin, Jessberger, Sebastian, Fendt, Sarah-Maria, Luttun, Aernout, Noel, Agns, Kiefer, Friedemann, Ghesquire, Bart, Moons, Lieve, Schoonjans, Luc, Dewerchin, Mieke, Eelen, Guy, Lambrechts, Diether, and Carmeliet, Peter

Subjects
Fatty acids -- Health aspects, Organogenesis -- Research, Biological research, Lymphatic vessels -- Physiological aspects, Biological oxidation (Metabolism) -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Lymphatic vessels are lined by lymphatic endothelial cells (LECs), and are critical for health. However, the role of metabolism in lymphatic development has not yet been elucidated. Here we report that in transgenic mouse models, LEC-specific loss of CPT1A, a rate-controlling enzyme in fatty acid -oxidation, impairs lymphatic development. LECs use fatty acid -oxidation to proliferate and for epigenetic regulation of lymphatic marker expression during LEC differentiation. Mechanistically, the transcription factor PROX1 upregulates CPT1A expression, which increases acetyl coenzyme A production dependent on fatty acid -oxidation. Acetyl coenzyme A is used by the histone acetyltransferase p300 to acetylate histones at lymphangiogenic genes. PROX1p300 interaction facilitates preferential histone acetylation at PROX1-target genes. Through this metabolism-dependent mechanism, PROX1 mediates epigenetic changes that promote lymphangiogenesis. Notably, blockade of CPT1 enzymes inhibits injury-induced lymphangiogenesis, and replenishing acetyl coenzyme A by supplementing acetate rescues this process in vivo., Author(s): Brian W. Wong [1, 2]; Xingwu Wang [1, 2]; Annalisa Zecchin [1, 2]; Bernard Thienpont [3, 4]; Ivo Cornelissen [1, 2]; Joanna Kalucka [1, 2]; Melissa Garca-Caballero [5]; Rindert [...]

Published
2017
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6. A genetic Xenopus laevis tadpole model to study lymphangiogenesis

Author

Ny, Annelii, Koch, Marta, Schneider, Martin, Neven, Elke, Tong, Ricky T, Maity, Sunit, Fischer, Christian, Plaisance, Stephane, Lambrechts, Diether, Heligon, Christophe, Terclavers, Sven, Ciesiolka, Malgorzata, Kalin, Roland, Man, Wing Yan, Senn, Irena, Wyns, Sabine, Lupu, Florea, Brandli, Andre, Vleminckx, Kris, Collen, Desire, Dewerchin, Mieke, Conway, Edward M, Moons, Lieve, Jain, Rakesh K, and Carmeliet, Peter

Abstract

Lymph vessels control fluid homeostasis, immunity and metastasis. Unraveling the molecular basis of lymphangiogenesis has been hampered by the lack of a small animal model that can be genetically manipulated. Here, we show that Xenopus tadpoles develop lymph vessels from lymphangioblasts or, through transdifferentiation, from venous endothelial cells. Lymphangiography showed that these lymph vessels drain lymph, through the lymph heart, to the venous circulation. Morpholino-mediated knockdown of the lymphangiogenic factor Prox1 caused lymph vessel defects and lymphedema by impairing lymphatic commitment. Knockdown of vascular endothelial growth factor C (VEGF-C) also induced lymph vessel defects and lymphedema, but primarily by affecting migration of lymphatic endothelial cells. Knockdown of VEGF-C also resulted in aberrant blood vessel formation in tadpoles. This tadpole model offers opportunities for the discovery of new regulators of lymphangiogenesis., Author(s): Annelii Ny [1, 5]; Marta Koch [1, 5]; Martin Schneider [1, 5]; Elke Neven [1, 5]; Ricky T Tong [2, 5]; Sunit Maity [1]; Christian Fischer [1]; Stephane Plaisance [...]

Published
2005
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8. Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex

Author

Bifari, Francesco, primary, Decimo, Ilaria, additional, Pino, Annachiara, additional, Llorens-Bobadilla, Enric, additional, Zhao, Sheng, additional, Lange, Christian, additional, Panuccio, Gabriella, additional, Boeckx, Bram, additional, Thienpont, Bernard, additional, Vinckier, Stefan, additional, Wyns, Sabine, additional, Bouché, Ann, additional, Lambrechts, Diether, additional, Giugliano, Michele, additional, Dewerchin, Mieke, additional, Martin-Villalba, Ana, additional, and Carmeliet, Peter, additional

Published
2017
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9. The role of fatty acid β-oxidation in lymphangiogenesis

Author

Wong, Brian W., primary, Wang, Xingwu, additional, Zecchin, Annalisa, additional, Thienpont, Bernard, additional, Cornelissen, Ivo, additional, Kalucka, Joanna, additional, García-Caballero, Melissa, additional, Missiaen, Rindert, additional, Huang, Hongling, additional, Brüning, Ulrike, additional, Blacher, Silvia, additional, Vinckier, Stefan, additional, Goveia, Jermaine, additional, Knobloch, Marlen, additional, Zhao, Hui, additional, Dierkes, Cathrin, additional, Shi, Chenyan, additional, Hägerling, René, additional, Moral-Dardé, Veronica, additional, Wyns, Sabine, additional, Lippens, Martin, additional, Jessberger, Sebastian, additional, Fendt, Sarah-Maria, additional, Luttun, Aernout, additional, Noel, Agnès, additional, Kiefer, Friedemann, additional, Ghesquière, Bart, additional, Moons, Lieve, additional, Schoonjans, Luc, additional, Dewerchin, Mieke, additional, Eelen, Guy, additional, Lambrechts, Diether, additional, and Carmeliet, Peter, additional

Published
2016
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10. HRG inhibits tumor growth and metastasis by inducing marcophage polarization and vessel normalization through downregulation of PIGF

Author

Charlotte Rolny, Massimiliano Mazzone, Sonia Tugues, Damya Laoui, Irja Johansson, Cathy Coulon, Mario Leonardo Squadrito, Immaculada Segura, Xiujuan Li, Ellen Knevels, Sandra Costa, Stefan Vinckier, Tom Dresselaer, Peter Akerud, Maria De Mol, Henrikka Salomaki, Mia Philipson, Wyns Sabine, Erik Larsson, Ian Buysschaert, Johan Botling, Uwe Himmelreich, Jo Van Ginderachter, Michele De Palma, Dewerchin, M., Lena Claesson-Welsh, Peter Carmeliet, Cellular and Molecular Immunology, and Department of Bio-engineering Sciences

Subjects
placental growth factor, tumor associated macrophages, metastasis, chemotherapy, histidine-rich glycoprotein
Abstract

Polarization of tumor-associated macrophages (TAMs) to a proangiogenic/immune-suppressive (M2-like) phenotype and abnormal, hypoperfused vessels are hallmarks of malignancy, but their molecular basis and interrelationship remains enigmatic. We report that the host-produced histidine-rich glycoprotein (HRG) inhibits tumor growth and metastasis, while improving chemotherapy. By skewing TAM polarization away from the M2- to a tumor-inhibiting M1-like phenotype, HRG promotes antitumor immune responses and vessel normalization, effects known to decrease tumor growth and metastasis and to enhance chemotherapy. Skewing of TAM polarization by HRG relies substantially on downregulation of placental growth factor (PlGF). Besides unveiling an important role forTAMpolarization in tumor vessel abnormalization, and its regulation by HRG/PlGF, these findings offer therapeutic opportunities for anticancer and antiangiogenic treatment.

Published
2011

11. Role of PFKFB3-driven glycolysis in vessel sprouting.

Author

UCL - SSS/DDUV - Institut de Duve, De Bock, Katrien, Georgiadou, Maria, Schoors, Sandra, Kuchnio, Anna, Wong, Brian W, Cantelmo, Anna Rita, Quaegebeur, Annelies, Ghesquière, Bart, Cauwenberghs, Sandra, Eelen, Guy, Phng, Li-Kun, Betz, Inge, Tembuyser, Bieke, Brepoels, Katleen, Welti, Jonathan, Geudens, Ilse, Segura, Inmaculada, Cruys, Bert, Bifari, Franscesco, Decimo, Ilaria, Blanco, Raquel, Wyns, Sabine, Vangindertael, Jeroen, Rocha, Susana, Collins, Russel T, Munck, Sebastian, Daelemans, Dirk, Imamura, Hiromi, Devlieger, Roland, Rider, Mark, Van Veldhoven, Paul P, Schuit, Frans, Bartrons, Ramon, Hofkens, Johan, Fraisl, Peter, Telang, Sucheta, Deberardinis, Ralph J, Schoonjans, Luc, Vinckier, Stefan, Chesney, Jason, Gerhardt, Holger, Dewerchin, Mieke, Carmeliet, Peter, UCL - SSS/DDUV - Institut de Duve, De Bock, Katrien, Georgiadou, Maria, Schoors, Sandra, Kuchnio, Anna, Wong, Brian W, Cantelmo, Anna Rita, Quaegebeur, Annelies, Ghesquière, Bart, Cauwenberghs, Sandra, Eelen, Guy, Phng, Li-Kun, Betz, Inge, Tembuyser, Bieke, Brepoels, Katleen, Welti, Jonathan, Geudens, Ilse, Segura, Inmaculada, Cruys, Bert, Bifari, Franscesco, Decimo, Ilaria, Blanco, Raquel, Wyns, Sabine, Vangindertael, Jeroen, Rocha, Susana, Collins, Russel T, Munck, Sebastian, Daelemans, Dirk, Imamura, Hiromi, Devlieger, Roland, Rider, Mark, Van Veldhoven, Paul P, Schuit, Frans, Bartrons, Ramon, Hofkens, Johan, Fraisl, Peter, Telang, Sucheta, Deberardinis, Ralph J, Schoonjans, Luc, Vinckier, Stefan, Chesney, Jason, Gerhardt, Holger, Dewerchin, Mieke, and Carmeliet, Peter

Abstract

Vessel sprouting by migrating tip and proliferating stalk endothelial cells (ECs) is controlled by genetic signals (such as Notch), but it is unknown whether metabolism also regulates this process. Here, we show that ECs relied on glycolysis rather than on oxidative phosphorylation for ATP production and that loss of the glycolytic activator PFKFB3 in ECs impaired vessel formation. Mechanistically, PFKFB3 not only regulated EC proliferation but also controlled the formation of filopodia/lamellipodia and directional migration, in part by compartmentalizing with F-actin in motile protrusions. Mosaic in vitro and in vivo sprouting assays further revealed that PFKFB3 overexpression overruled the pro-stalk activity of Notch, whereas PFKFB3 deficiency impaired tip cell formation upon Notch blockade, implying that glycolysis regulates vessel branching.

Published
2013

12. Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization

Author

UCL - MD/FARM - Ecole de pharmacie, UCL - (SLuc) Service de médecine nucléaire, Mazzone, Massimiliano, Dettori, Daniela, Leite de Oliveira, Rodrigo, Loges, Sonja, Schmidt, Thomas, Jonckx, Bart, Tian, Ya-Min, Lanahan, Anthony A., Pollard, Patrick, Ruiz de Almodovar, Carmen, De Smet, Frederik, Vinckier, Stefan, Aragonés, Julián, Debackere, Koen, Luttun, Aernout, Wyns, Sabine, Jordan, Bénédicte, Pisacane, Alberto, Gallez, Bernard, Lampugnani, Maria Grazia, Dejana, Elisabetta, Simons, Michael, Ratcliffe, Peter, Maxwell, Patrick, Carmeliet, Peter, UCL - MD/FARM - Ecole de pharmacie, UCL - (SLuc) Service de médecine nucléaire, Mazzone, Massimiliano, Dettori, Daniela, Leite de Oliveira, Rodrigo, Loges, Sonja, Schmidt, Thomas, Jonckx, Bart, Tian, Ya-Min, Lanahan, Anthony A., Pollard, Patrick, Ruiz de Almodovar, Carmen, De Smet, Frederik, Vinckier, Stefan, Aragonés, Julián, Debackere, Koen, Luttun, Aernout, Wyns, Sabine, Jordan, Bénédicte, Pisacane, Alberto, Gallez, Bernard, Lampugnani, Maria Grazia, Dejana, Elisabetta, Simons, Michael, Ratcliffe, Peter, Maxwell, Patrick, and Carmeliet, Peter

Abstract

A key function of blood vessels, to supply oxygen, is impaired in tumors because of abnormalities in their endothelial lining. PHD proteins serve as oxygen sensors and may regulate oxygen delivery. We therefore studied the role of endothelial PHD2 in vessel shaping by implanting tumors in PHD2(+/-) mice. Haplodeficiency of PHD2 did not affect tumor vessel density or lumen size, but normalized the endothelial lining and vessel maturation. This resulted in improved tumor perfusion and oxygenation and inhibited tumor cell invasion, intravasation, and metastasis. Haplodeficiency of PHD2 redirected the specification of endothelial tip cells to a more quiescent cell type, lacking filopodia and arrayed in a phalanx formation. This transition relied on HIF-driven upregulation of (soluble) VEGFR-1 and VE-cadherin. Thus, decreased activity of an oxygen sensor in hypoxic conditions prompts endothelial cells to readjust their shape and phenotype to restore oxygen supply. Inhibition of PHD2 may offer alternative therapeutic opportunities for anticancer therapy.

Published
2009

13. Peroxisomal multifunctional protein-2 deficiency causes neuroinflammation and degeneration of Purkinje cells independent of very long chain fatty acid accumulation

Author

Verheijden, Simon, primary, Bottelbergs, Astrid, additional, Krysko, Olga, additional, Krysko, Dmitri V., additional, Beckers, Lien, additional, De Munter, Stephanie, additional, Van Veldhoven, Paul P., additional, Wyns, Sabine, additional, Kulik, Wim, additional, Nave, Klaus-Armin, additional, Ramer, Matt S., additional, Carmeliet, Peter, additional, Kassmann, Celia M., additional, and Baes, Myriam, additional

Published
2013
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14. Role of PFKFB3-Driven Glycolysis in Vessel Sprouting

Author

De Bock, Katrien, primary, Georgiadou, Maria, additional, Schoors, Sandra, additional, Kuchnio, Anna, additional, Wong, Brian W., additional, Cantelmo, Anna Rita, additional, Quaegebeur, Annelies, additional, Ghesquière, Bart, additional, Cauwenberghs, Sandra, additional, Eelen, Guy, additional, Phng, Li-Kun, additional, Betz, Inge, additional, Tembuyser, Bieke, additional, Brepoels, Katleen, additional, Welti, Jonathan, additional, Geudens, Ilse, additional, Segura, Inmaculada, additional, Cruys, Bert, additional, Bifari, Franscesco, additional, Decimo, Ilaria, additional, Blanco, Raquel, additional, Wyns, Sabine, additional, Vangindertael, Jeroen, additional, Rocha, Susana, additional, Collins, Russel T., additional, Munck, Sebastian, additional, Daelemans, Dirk, additional, Imamura, Hiromi, additional, Devlieger, Roland, additional, Rider, Mark, additional, Van Veldhoven, Paul P., additional, Schuit, Frans, additional, Bartrons, Ramon, additional, Hofkens, Johan, additional, Fraisl, Peter, additional, Telang, Sucheta, additional, DeBerardinis, Ralph J., additional, Schoonjans, Luc, additional, Vinckier, Stefan, additional, Chesney, Jason, additional, Gerhardt, Holger, additional, Dewerchin, Mieke, additional, and Carmeliet, Peter, additional

Published
2013
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15. Heterozygous Deficiency of PHD2 Restores Tumor Oxygenation and Inhibits Metastasis via Endothelial Normalization

Author

Mazzone, Massimiliano, primary, Dettori, Daniela, additional, Leite de Oliveira, Rodrigo, additional, Loges, Sonja, additional, Schmidt, Thomas, additional, Jonckx, Bart, additional, Tian, Ya-Min, additional, Lanahan, Anthony A., additional, Pollard, Patrick, additional, Ruiz de Almodovar, Carmen, additional, De Smet, Frederik, additional, Vinckier, Stefan, additional, Aragonés, Julián, additional, Debackere, Koen, additional, Luttun, Aernout, additional, Wyns, Sabine, additional, Jordan, Benedicte, additional, Pisacane, Alberto, additional, Gallez, Bernard, additional, Lampugnani, Maria Grazia, additional, Dejana, Elisabetta, additional, Simons, Michael, additional, Ratcliffe, Peter, additional, Maxwell, Patrick, additional, and Carmeliet, Peter, additional

Published
2009
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17. Anti-PlGF Inhibits Growth of VEGF(R)-Inhibitor-Resistant Tumors without Affecting Healthy Vessels

Author

Fischer, Christian, primary, Jonckx, Bart, additional, Mazzone, Massimiliano, additional, Zacchigna, Serena, additional, Loges, Sonja, additional, Pattarini, Lucia, additional, Chorianopoulos, Emmanuel, additional, Liesenborghs, Laurens, additional, Koch, Marta, additional, De Mol, Maria, additional, Autiero, Monica, additional, Wyns, Sabine, additional, Plaisance, Stephane, additional, Moons, Lieve, additional, van Rooijen, Nico, additional, Giacca, Mauro, additional, Stassen, Jean-Marie, additional, Dewerchin, Mieke, additional, Collen, Desire, additional, and Carmeliet, Peter, additional

Published
2007
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18. VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain

Author

Le Bras, Barbara, primary, Barallobre, Maria-José, additional, Homman-Ludiye, Jihane, additional, Ny, Annelii, additional, Wyns, Sabine, additional, Tammela, Tuomas, additional, Haiko, Paula, additional, Karkkainen, Marika J, additional, Yuan, Li, additional, Muriel, Marie-Paule, additional, Chatzopoulou, Elli, additional, Bréant, Christiane, additional, Zalc, Bernard, additional, Carmeliet, Peter, additional, Alitalo, Kari, additional, Eichmann, Anne, additional, and Thomas, Jean-Léon, additional

Published
2006
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19. VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death

Author

Lambrechts, Diether, primary, Storkebaum, Erik, additional, Morimoto, Masafumi, additional, Del-Favero, Jurgen, additional, Desmet, Frederik, additional, Marklund, Stefan L, additional, Wyns, Sabine, additional, Thijs, Vincent, additional, Andersson, Jörgen, additional, van Marion, Ingrid, additional, Al-Chalabi, Ammar, additional, Bornes, Stephanie, additional, Musson, Rhiannon, additional, Hansen, Valerie, additional, Beckman, Lars, additional, Adolfsson, Rolf, additional, Pall, Hardev Singh, additional, Prats, Hervé, additional, Vermeire, Severine, additional, Rutgeerts, Paul, additional, Katayama, Shigehiro, additional, Awata, Takuya, additional, Leigh, Nigel, additional, Lang-Lazdunski, Loïc, additional, Dewerchin, Mieke, additional, Shaw, Christopher, additional, Moons, Lieve, additional, Vlietinck, Robert, additional, Morrison, Karen E, additional, Robberecht, Wim, additional, Van Broeckhoven, Christine, additional, Collen, Désiré, additional, Andersen, Peter M, additional, and Carmeliet, Peter, additional

Published
2003
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20. Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS.

Author

Storkebaum, Erik, Lambrechts, Diether, Dewerchin, Mieke, Moreno-Murciano, Maria-Paz, Appelmans, Saskia, Oh, Hideyasu, Van Damme, Philip, Rutten, Bart, Man, Wing Yan, De Mol, Maria, Wyns, Sabine, Manka, David, Vermeulen, Kristel, Van Den Bosch, Ludo, Mertens, Nico, Schmitz, Christoph, Robberecht, Wim, Conway, Edward M, Collen, D&aeacute;sir&aeacute;, and Moons, Lieve

Subjects
AMYOTROPHIC lateral sclerosis, DISEASES, NEURODEGENERATION, NEUROMUSCULAR diseases, CYTOKINES, MYONEURAL junction
Abstract

Neurotrophin treatment has so far failed to prolong the survival of individuals affected with amyotrophic lateral sclerosis (ALS), an incurable motoneuron degenerative disorder. Here we show that intracerebroventricular (i.c.v.) delivery of recombinant vascular endothelial growth factor (Vegf) in a SOD1G93A rat model of ALS delays onset of paralysis by 17 d, improves motor performance and prolongs survival by 22 d, representing the largest effects in animal models of ALS achieved by protein delivery. By protecting cervical motoneurons, i.c.v. delivery of Vegf is particularly effective in rats with the most severe form of ALS with forelimb onset. Vegf has direct neuroprotective effects on motoneurons in vivo, because neuronal expression of a transgene expressing the Vegf receptor prolongs the survival of SOD1G93A mice. On i.c.v. delivery, Vegf is anterogradely transported and preserves neuromuscular junctions in SOD1G93A rats. Our findings in preclinical rodent models of ALS may have implications for treatment of neurodegenerative disease in general. [ABSTRACT FROM AUTHOR]

Published
2005
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21. HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF

Author

Rolny, Charlotte, Mazzone, Massimiliano, Tugues, Sònia, Laoui, Damya, Johansson, Irja, Coulon, Cathy, Squadrito, Mario Leonardo, Segura, Inmaculada, Li, Xiujuan, Knevels, Ellen, Costa, Sandra, Vinckier, Stefan, Dresselaer, Tom, Åkerud, Peter, De Mol, Maria, Salomäki, Henriikka, Phillipson, Mia, Wyns, Sabine, Larsson, Erik, Buysschaert, Ian, Botling, Johan, Himmelreich, Uwe, Ginderachter, Van, Jo, A., De Palma, Michele, Dewerchin, Mieke, Claesson-Welsh, Lena, and Carmeliet, Peter

Abstract

Polarization of tumor-associated macrophages (TAMs) to a proangiogenic/immune-suppressive (M2-like) phenotype and abnormal, hypoperfused vessels are hallmarks of malignancy, but their molecular basis and interrelationship remains enigmatic. We report that the host-produced histidine-rich glycoprotein (HRG) inhibits tumor growth and metastasis, while improving chemotherapy. By skewing TAM polarization away from the M2- to a tumor-inhibiting M1-like phenotype, HRG promotes antitumor immune responses and vessel normalization, effects known to decrease tumor growth and metastasis and to enhance chemotherapy. Skewing of TAM polarization by HRG relies substantially on downregulation of placental growth factor (PlGF). Besides unveiling an important role for TAM polarization in tumor vessel abnormalization, and its regulation by HRG/PlGF, these findings offer therapeutic opportunities for anticancer and antiangiogenic treatment.

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