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CD90 Expression Controls Migration and Predicts Dasatinib Response in Glioblastoma

Abstract : Purpose: CD90 (Thy-1) is a glycophosphatidylinositol-anchored glycoprotein considered as a surrogate marker for a variety of stem cells, including glioblastoma (GBM) stem cells (GSC). However, the molecular and cellular functions of CD90 remain unclear.Experimental Design: The function of CD90 in GBM was addressed using cellular models from immortalized and primary GBMlines, in vivo orthotopic mouse models, and GBM specimens' transcriptome associated with MRI features from GBM patients. CD90 expression was silenced in U251 and GBM primary cells and complemented in CD90-negative U87 cells.Results: We showed that CD90 is not only expressed on GSCs but also on more differentiated GBM cancer cells. In GBM patients, CD90 expression was associated with an adhesion/migration gene signature and with invasive tumor features. Modulation of CD90 expression in GBM cells dramatically affected their adhesion and migration properties. Moreover, orthotopic xenografts revealed that CD90 expression induced invasive phenotypes in vivo. Indeed, CD90 expression led to enhanced SRC and FAK signaling in our GBM cellular models and GBM patients' specimens. Pharmacologic inhibition of these signaling nodes blunted adhesion and migration in CD90-positive cells. Remarkably, dasatinib blunted CD90-dependent GBM cell invasion in vivo and killed CD90(high) primary GSC lines.Conclusions: Our data demonstrate that CD90 is an actor of GBM invasiveness through SRC-dependent mechanisms and could be used as a predictive factor for dasatinib response in CD90high GBM patients. (C) 2017 AACR.
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Submitted on : Thursday, March 15, 2018 - 11:19:02 AM
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Tony Avril, Amandine Etcheverry, Raphael Pineau, Joanna Obacz, Gwenaele Jegou, et al.. CD90 Expression Controls Migration and Predicts Dasatinib Response in Glioblastoma. Clinical Cancer Research, American Association for Cancer Research, 2017, 23 (23), pp.7360-7374. ⟨10.1158/1078-0432.CCR-17-1549⟩. ⟨hal-01671761⟩

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