Les cellules initiatrices de tumeurs à l'origine de l'hétérogénéité d'expression de l'intégrine α5β1 dans les glioblastomes

Abstract : Glioblastoma (GBM) is the most aggressive primary brain tumor. Treatment failure is explained by inter and intratumoral heterogeneity. Our previous results showed that the α5β1 integrin, the fibronectin receptor, is implicated in GBM aggressiveness. We observed that its expression was heterogeneous between patients' tumors but also between different areas in a given tumor. We hypothesized that this heterogeneity may be linked to different glioma stem cells (GSC). We confirmed that α5 expression is induced after differentiation in about half of the cell lines supporting the notion of inter-tumoral heterogeneity. We also observed with single cell-derived clone analysis that intra-tumoral GICs heterogeneity exists. We noticed that when GICs are programmed to express α5 integrin, differentiated cells become more aggressive. Our data support that differentiated cells expressing the integrin have an increased capacity of proliferation and acquire a fibronectin-dependent motility and a resistance phenotype. This work provides a better understanding of the origin of more aggressive foci and highlights the interest of α5β1 integrin as a therapeutic target for a subpopulation of patients.
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Marie-Cécile Mercier. Les cellules initiatrices de tumeurs à l'origine de l'hétérogénéité d'expression de l'intégrine α5β1 dans les glioblastomes. Biologie cellulaire. Université de Strasbourg, 2018. Français. ⟨NNT : 2018STRAJ100⟩. ⟨tel-02303810⟩

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