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Soluble CD146, a biomarker and a target for preventing resistance to anti-angiogenic therapy in glioblastoma
RATIONALE: Glioblastoma multiforme (GBM) is a primary brain tumor with poor prognosis. The U.S. food and drug administration approved the use of the anti-VEGF antibody bevacizumab in recurrent GBM. However, resistance to this treatment is frequent and fails to enhance the overall survival of patient...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9590138/ https://www.ncbi.nlm.nih.gov/pubmed/36274147 http://dx.doi.org/10.1186/s40478-022-01451-3 |
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author | Joshkon, Ahmad Tabouret, Emeline Traboulsi, Wael Bachelier, Richard Simoncini, Stéphanie Roffino, Sandrine Jiguet-Jiglaire, Carine Badran, Bassam Guillet, Benjamin Foucault-Bertaud, Alexandrine Leroyer, Aurelie S. Dignat-George, Françoise Chinot, Olivier Fayyad-Kazan, Hussein Bardin, Nathalie Blot-Chabaud, Marcel |
author_facet | Joshkon, Ahmad Tabouret, Emeline Traboulsi, Wael Bachelier, Richard Simoncini, Stéphanie Roffino, Sandrine Jiguet-Jiglaire, Carine Badran, Bassam Guillet, Benjamin Foucault-Bertaud, Alexandrine Leroyer, Aurelie S. Dignat-George, Françoise Chinot, Olivier Fayyad-Kazan, Hussein Bardin, Nathalie Blot-Chabaud, Marcel |
author_sort | Joshkon, Ahmad |
collection | PubMed |
description | RATIONALE: Glioblastoma multiforme (GBM) is a primary brain tumor with poor prognosis. The U.S. food and drug administration approved the use of the anti-VEGF antibody bevacizumab in recurrent GBM. However, resistance to this treatment is frequent and fails to enhance the overall survival of patients. In this study, we aimed to identify novel mechanism(s) responsible for bevacizumab-resistance in CD146-positive glioblastoma. METHODS: The study was performed using sera from GBM patients and human GBM cell lines in culture or xenografted in nude mice. RESULTS: We found that an increase in sCD146 concentration in sera of GBM patients after the first cycle of bevacizumab treatment was significantly associated with poor progression free survival and shorter overall survival. Accordingly, in vitro treatment of CD146-positive glioblastoma cells with bevacizumab led to a high sCD146 secretion, inducing cell invasion. These effects were mediated through integrin αvβ3 and were blocked by mucizumab, a novel humanized anti-sCD146 antibody. In vivo, the combination of bevacizumab with mucizumab impeded CD146 + glioblastoma growth and reduced tumor cell dissemination to an extent significantly higher than that observed with bevacizumab alone. CONCLUSION: We propose sCD146 to be 1/ an early biomarker to predict and 2/ a potential target to prevent bevacizumab resistance in patients with glioblastoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-022-01451-3. |
format | Online Article Text |
id | pubmed-9590138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-95901382022-10-25 Soluble CD146, a biomarker and a target for preventing resistance to anti-angiogenic therapy in glioblastoma Joshkon, Ahmad Tabouret, Emeline Traboulsi, Wael Bachelier, Richard Simoncini, Stéphanie Roffino, Sandrine Jiguet-Jiglaire, Carine Badran, Bassam Guillet, Benjamin Foucault-Bertaud, Alexandrine Leroyer, Aurelie S. Dignat-George, Françoise Chinot, Olivier Fayyad-Kazan, Hussein Bardin, Nathalie Blot-Chabaud, Marcel Acta Neuropathol Commun Research RATIONALE: Glioblastoma multiforme (GBM) is a primary brain tumor with poor prognosis. The U.S. food and drug administration approved the use of the anti-VEGF antibody bevacizumab in recurrent GBM. However, resistance to this treatment is frequent and fails to enhance the overall survival of patients. In this study, we aimed to identify novel mechanism(s) responsible for bevacizumab-resistance in CD146-positive glioblastoma. METHODS: The study was performed using sera from GBM patients and human GBM cell lines in culture or xenografted in nude mice. RESULTS: We found that an increase in sCD146 concentration in sera of GBM patients after the first cycle of bevacizumab treatment was significantly associated with poor progression free survival and shorter overall survival. Accordingly, in vitro treatment of CD146-positive glioblastoma cells with bevacizumab led to a high sCD146 secretion, inducing cell invasion. These effects were mediated through integrin αvβ3 and were blocked by mucizumab, a novel humanized anti-sCD146 antibody. In vivo, the combination of bevacizumab with mucizumab impeded CD146 + glioblastoma growth and reduced tumor cell dissemination to an extent significantly higher than that observed with bevacizumab alone. CONCLUSION: We propose sCD146 to be 1/ an early biomarker to predict and 2/ a potential target to prevent bevacizumab resistance in patients with glioblastoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-022-01451-3. BioMed Central 2022-10-23 /pmc/articles/PMC9590138/ /pubmed/36274147 http://dx.doi.org/10.1186/s40478-022-01451-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Joshkon, Ahmad Tabouret, Emeline Traboulsi, Wael Bachelier, Richard Simoncini, Stéphanie Roffino, Sandrine Jiguet-Jiglaire, Carine Badran, Bassam Guillet, Benjamin Foucault-Bertaud, Alexandrine Leroyer, Aurelie S. Dignat-George, Françoise Chinot, Olivier Fayyad-Kazan, Hussein Bardin, Nathalie Blot-Chabaud, Marcel Soluble CD146, a biomarker and a target for preventing resistance to anti-angiogenic therapy in glioblastoma |
title | Soluble CD146, a biomarker and a target for preventing resistance to anti-angiogenic therapy in glioblastoma |
title_full | Soluble CD146, a biomarker and a target for preventing resistance to anti-angiogenic therapy in glioblastoma |
title_fullStr | Soluble CD146, a biomarker and a target for preventing resistance to anti-angiogenic therapy in glioblastoma |
title_full_unstemmed | Soluble CD146, a biomarker and a target for preventing resistance to anti-angiogenic therapy in glioblastoma |
title_short | Soluble CD146, a biomarker and a target for preventing resistance to anti-angiogenic therapy in glioblastoma |
title_sort | soluble cd146, a biomarker and a target for preventing resistance to anti-angiogenic therapy in glioblastoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9590138/ https://www.ncbi.nlm.nih.gov/pubmed/36274147 http://dx.doi.org/10.1186/s40478-022-01451-3 |
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