Caveolin-1 regulates glioblastoma aggressiveness through the control of α 5β 1 integrin expression and modulates glioblastoma responsiveness to SJ749, an α 5β 1 integrin antagonist

Abstract

Caveolin-1 plays a checkpoint function in the regulation of processes often altered in cancer. Although increased expression of caveolin-1 seems to be the norm in the glioma family of malignancies, populations of caveolin-1 positive and negative cells coexist among glioblastoma specimens. As no data are available to date on the contribution of such cells to the phenotype of glioblastoma, we manipulated caveolin-1 in the glioblastoma cell line U87MG. We showed that caveolin-1 plays a critical role in the aggressiveness of glioblastoma. We identified integrins as the main set of genes affected by caveolin-1. We reported here that the phenotypic changes observed after caveolin-1 modulation were mediated by α 5β 1 integrins. As a consequence of the regulation of α 5β 1 levels by caveolin-1, the sensitivity of cells to the specific α 5β 1 integrin antagonist, SJ749, was affected. Mediator of caveolin-1 effects, α 5β 1 integrin, is also a marker for glioma aggressiveness and an efficient target for the treatment of glioma especially the ones exerting the highest aggressive phenotype.