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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23189121/?tool=EBI |
| _version_ | 1818426507987517440 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T14:30:56Z |
| format | Article |
| id | doaj.art-744a37d030464bac94fddfaa1b125e3b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T14:30:56Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-744a37d030464bac94fddfaa1b125e3b2022-12-21T22:57:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e4542310.1371/journal.pone.0045423Anti-Gb3 monoclonal antibody inhibits angiogenesis and tumor development.Ariane DesselleTanguy ChaumetteMarie-Hélène GauglerDenis CochonneauJulien FleurenceNolwenn DuboisPhilippe HulinJacques AubryStéphane BirkléFrançois ParisInhibiting 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23189121/?tool=EBI |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | Anti-Gb3 monoclonal antibody inhibits angiogenesis and tumor development. |
| title_sort | anti gb3 monoclonal antibody inhibits angiogenesis and tumor development |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23189121/?tool=EBI |
| work_keys_str_mv | AT arianedesselle antigb3monoclonalantibodyinhibitsangiogenesisandtumordevelopment AT tanguychaumette antigb3monoclonalantibodyinhibitsangiogenesisandtumordevelopment AT mariehelenegaugler antigb3monoclonalantibodyinhibitsangiogenesisandtumordevelopment AT deniscochonneau antigb3monoclonalantibodyinhibitsangiogenesisandtumordevelopment AT julienfleurence antigb3monoclonalantibodyinhibitsangiogenesisandtumordevelopment AT nolwenndubois antigb3monoclonalantibodyinhibitsangiogenesisandtumordevelopment AT philippehulin antigb3monoclonalantibodyinhibitsangiogenesisandtumordevelopment AT jacquesaubry antigb3monoclonalantibodyinhibitsangiogenesisandtumordevelopment AT stephanebirkle antigb3monoclonalantibodyinhibitsangiogenesisandtumordevelopment AT francoisparis antigb3monoclonalantibodyinhibitsangiogenesisandtumordevelopment |