CD90 expression controls migration and predicts dasatinib response in glioblastoma

Tony Avril, Amandine Etcheverry, Raphaël Pineau, Joanna Obacz, Gwénaële Jegou, Florence Jouan, Pierre Jean Le Reste, Masumeh Hatami, Rivka R. Colen, Brett L. Carlson, Paul A. Decker, Jann N Sarkaria, Elodie Vauléon, Dan Cristian Chiforeanu, Anne Clavreul, Jean Mosser, Eric Chevet, Véronique Quillien

Research output: Contribution to journalArticle

6 Scopus citations

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 GBM lines, 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 CD90high 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.

Original languageEnglish (US)
Pages (from-to)7360-7374
Number of pages15
JournalClinical Cancer Research
Volume23
Issue number23
DOIs
StatePublished - Dec 1 2017

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Avril, T., Etcheverry, A., Pineau, R., Obacz, J., Jegou, G., Jouan, F., Le Reste, P. J., Hatami, M., Colen, R. R., Carlson, B. L., Decker, P. A., Sarkaria, J. N., Vauléon, E., Chiforeanu, D. C., Clavreul, A., Mosser, J., Chevet, E., & Quillien, V. (2017). CD90 expression controls migration and predicts dasatinib response in glioblastoma. Clinical Cancer Research, 23(23), 7360-7374. https://doi.org/10.1158/1078-0432.CCR-17-1549