Soluble CD146, a biomarker and a target for preventing resistance to anti-angiogenic therapy in glioblastoma.
Bevacizumab
Biomarker
Glioblastoma
Soluble CD146
Therapeutic antibody
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
23 10 2022
23 10 2022
Historique:
received:
23
06
2022
accepted:
28
09
2022
entrez:
24
10
2022
pubmed:
25
10
2022
medline:
26
10
2022
Statut:
epublish
Résumé
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. The study was performed using sera from GBM patients and human GBM cell lines in culture or xenografted in nude mice. 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. We propose sCD146 to be 1/ an early biomarker to predict and 2/ a potential target to prevent bevacizumab resistance in patients with glioblastoma.
Identifiants
pubmed: 36274147
doi: 10.1186/s40478-022-01451-3
pii: 10.1186/s40478-022-01451-3
pmc: PMC9590138
doi:
Substances chimiques
Bevacizumab
2S9ZZM9Q9V
CD146 Antigen
0
Integrin alphaVbeta3
0
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
151Informations de copyright
© 2022. The Author(s).
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