journal contribution
posted on 2023-03-31, 20:26 authored by 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 Figure S1: CD90 mRNA expression on NCI and glioma cell lines, glioma and GBM specimens; Figure S2: CD90 mRNA and protein are expressed on all GBM cells; Figure S3: Expression of adhesion/migration genes in CD90low and CD90high RNS cell lines and EMT associated genes in CD90low and CD90high GBM patients; Figure S4: CD90 affects cell-cell/matrix adhesion of U251 and U87 GBM cell lines; Figure S5: CD90 affects migration of U251, U87 and primary GBM cell lines; Figure S6: CD90 signaling involves SRC and FAK kinases; Figure S7: CD90-dependent migration involves MEK1, Rac1 and JNK signaling molecules; TABLE S1: Patients demographic and clinical characteristics; TABLE S2: Top10 genes up-regulated in CD90low and CD90high GBM patients1.
Funding
la Ligue Contre le Cancer Comité d'Ille-et-Villaine
d'Indre-et-Loire et du Morbihan
Centre Eugène Marquis
Ligue Contre le Cancer
l'Institut National du Cancer
History
ARTICLE 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. Clin Cancer Res; 23(23); 7360–74. ©2017 AACR.
