CD90 Expression Controls Migration and Predicts Dasatinib Response in Glioblastoma

Abstract

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. The function of CD90 in GBM was addressed using cellular models from immortalized and primary GBM lines, 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. 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 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 and killed CD90 primary GSC lines. 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 CD90 GBM patients. .

Endothelial, pericyte and tumor cell expression in glioblastoma identifies fibroblast activation protein (FAP) as an excellent target for immunotherapy

“…Furthermore, we conclude that the most likely identity of the CD45 -CD31 -PDGFRbpopulation is tumor cells, with a subset expressing CD90 as previously described. [44][45][46] The expression of FAP within each of the six identified cell types is shown in Figure 6b cytometry was lower than that detected by scRNAseq, especially for specimen BT26. Also, for specimen BT23, FAP transcripts were detected within some of the GAMs by scRNAseq but these cells completely lacked detectable FAP in the flow cytometry analysis.…”

The expression of EMX2 lead to cell cycle arrest in glioblastoma cell line

“…Tumors used in this study were histologically diagnosed as grade IV astrocytoma according to WHO criteria. Adherent (RADH) and neurospheres (RNS) (enriched in stem cells) GB primary cell lines were obtained from GB samples as described in [ 32 , 33 ]. Briefly, fresh tumor tissue was mechanically dissociated using gentleMACS dissociator following manufacturer’s instructions (Miltenyi Biotec).…”

Crocetin Extracted from Saffron Shows Antitumor Effects in Models of Human Glioblastoma

“…CD44 is related to epithelial-mesenchymal transition (EMT) and contributes to the invasive capacity, the formation of metastases, and resistance to therapy [5]. The CD90 glycoprotein is commonly used as a marker of EMT and mesenchymal cells, but it is also identifiable in differentiated GBM cancer cells [7]; the molecular and cellular functions of CD90 are not yet clarified. Regardless, the modulation of CD90 expression dramatically influences cell adhesion, migration, and invasiveness of GBM cells, thereby contributing to the onset of a malignant phenotype.…”