Anti-Gb3 monoclonal antibody inhibits angiogenesis and tumor development.

Inhibiting the growth of tumor vasculature represents one of the relevant strategies against tumor progression. Between all the different pro-angiogenic molecular targets, plasma membrane glycosphingolipids have been under-investigated. In this present study, we explore the anti-angiogenic therapeut...

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Autores principales:	Ariane Desselle, Tanguy Chaumette, Marie-Hélène Gaugler, Denis Cochonneau, Julien Fleurence, Nolwenn Dubois, Philippe Hulin, Jacques Aubry, Stéphane Birklé, François Paris
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/744a37d030464bac94fddfaa1b125e3b
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spelling	oai:doaj.org-article:744a37d030464bac94fddfaa1b125e3b2021-11-18T08:07:40ZAnti-Gb3 monoclonal antibody inhibits angiogenesis and tumor development.1932-620310.1371/journal.pone.0045423https://doaj.org/article/744a37d030464bac94fddfaa1b125e3b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23189121/?tool=EBIhttps://doaj.org/toc/1932-6203Inhibiting the growth of tumor vasculature represents one of the relevant strategies against tumor progression. Between all the different pro-angiogenic molecular targets, plasma membrane glycosphingolipids have been under-investigated. In this present study, we explore the anti-angiogenic therapeutic advantage of a tumor immunotherapy targeting the globotriaosylceramide Gb3. In this purpose, a monoclonal antibody against Gb3, named 3E2 was developed and characterized. We first demonstrate that Gb3 is over-expressed in proliferative endothelial cells relative to quiescent cells. Then, we demonstrate that 3E2 inhibits endothelial cell proliferation in vitro by slowing endothelial cell proliferation and by increasing mitosis duration. Antibody 3E2 is further effective in inhibiting ex vivo angiogenesis in aorta ring assays. Moreover, 3E2 treatment inhibits NXS2 neuroblastoma development and liver metastases spreading in A/J mice. Immunohistology examination of the NXS2 metastases shows that only endothelial cells, but not cancer cells express Gb3. Finally, 3E2 treatment diminishes tumor vessels density, proving a specific therapeutic action of our monoclonal antibody to tumor vasculature. Our study demonstrates that Gb3 is a viable alternative target for immunotherapy and angiogenesis inhibition.Ariane DesselleTanguy ChaumetteMarie-Hélène GauglerDenis CochonneauJulien FleurenceNolwenn DuboisPhilippe HulinJacques AubryStéphane BirkléFrançois ParisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e45423 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ariane Desselle Tanguy Chaumette Marie-Hélène Gaugler Denis Cochonneau Julien Fleurence Nolwenn Dubois Philippe Hulin Jacques Aubry Stéphane Birklé François Paris Anti-Gb3 monoclonal antibody inhibits angiogenesis and tumor development.
description	Inhibiting the growth of tumor vasculature represents one of the relevant strategies against tumor progression. Between all the different pro-angiogenic molecular targets, plasma membrane glycosphingolipids have been under-investigated. In this present study, we explore the anti-angiogenic therapeutic advantage of a tumor immunotherapy targeting the globotriaosylceramide Gb3. In this purpose, a monoclonal antibody against Gb3, named 3E2 was developed and characterized. We first demonstrate that Gb3 is over-expressed in proliferative endothelial cells relative to quiescent cells. Then, we demonstrate that 3E2 inhibits endothelial cell proliferation in vitro by slowing endothelial cell proliferation and by increasing mitosis duration. Antibody 3E2 is further effective in inhibiting ex vivo angiogenesis in aorta ring assays. Moreover, 3E2 treatment inhibits NXS2 neuroblastoma development and liver metastases spreading in A/J mice. Immunohistology examination of the NXS2 metastases shows that only endothelial cells, but not cancer cells express Gb3. Finally, 3E2 treatment diminishes tumor vessels density, proving a specific therapeutic action of our monoclonal antibody to tumor vasculature. Our study demonstrates that Gb3 is a viable alternative target for immunotherapy and angiogenesis inhibition.
format	article
author	Ariane Desselle Tanguy Chaumette Marie-Hélène Gaugler Denis Cochonneau Julien Fleurence Nolwenn Dubois Philippe Hulin Jacques Aubry Stéphane Birklé François Paris
author_facet	Ariane Desselle Tanguy Chaumette Marie-Hélène Gaugler Denis Cochonneau Julien Fleurence Nolwenn Dubois Philippe Hulin Jacques Aubry Stéphane Birklé François Paris
author_sort	Ariane Desselle
title	Anti-Gb3 monoclonal antibody inhibits angiogenesis and tumor development.
title_short	Anti-Gb3 monoclonal antibody inhibits angiogenesis and tumor development.
title_full	Anti-Gb3 monoclonal antibody inhibits angiogenesis and tumor development.
title_fullStr	Anti-Gb3 monoclonal antibody inhibits angiogenesis and tumor development.
title_full_unstemmed	Anti-Gb3 monoclonal antibody inhibits angiogenesis and tumor development.
title_sort	anti-gb3 monoclonal antibody inhibits angiogenesis and tumor development.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/744a37d030464bac94fddfaa1b125e3b
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Anti-Gb3 monoclonal antibody inhibits angiogenesis and tumor development.

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