Plasma Extracellular Vesicles from Glioblastoma Patients Affect Phenotype and Activate Receptor Tyrosine Kinases in Glioblastoma Cells.

Extracellular vesicles are important transmitters of oncogenic signals between cancer cells. Despite numerous studies of vesicles from model glioblastoma (GBM) cells, information on the effects of vesicles from GBM patients on the development of model GB cells is lacking. In this study, plasma vesicles from healthy donors (HVs) and GBM patients (GVs) were studied to affect expression of differentiation (GFAP and GLT-1) and stemness (CD9 and CD133) markers and expression and activation of the oncogenic receptor tyrosine kinases EGFR and PDGFRβ in GBM cells (primary GBM011 and model U251 MG cell lines) and rat and human normal astrocytes. GVs reduced GFAP expression in GBM011 cells and stimulated GFAP and CD9 expression in U251 MG cells. GVs increased EGFR and PDGFRβ expression in both GBM cell lines and enhanced EGFR (Y1086) and PDGFRβ (Y751) phosphorylation in U251 MG cells. HVs stimulated CD9 expression in U251 MG cells and PDGFRβ expression in GBM011 cells, but decreased EGFR and PDGFRβ expression in U251 MG cells. Thus, both GVs and HVs influence the GBM phenotype and receptor tyrosine kinase activation.