Temozolomide Increases HSPs in Extracellular Vesicles Released from Glioblastoma Cells

Abstract

Glioblastoma (GBM) is the most malignant and the fastest-progressing type of primary brain tumours. Temozolomide (TMZ) is a chemotherapeutic drug for the treatment of GBM. Extracellular vesicles (EVs) have been recently confirmed to have a substantial role in the GBM, and their contents released from GBM cells have been considered a target for treatment. Here, we assessed the impact of TMZ on heat shock proteins (HSPs) derived from extracellular vesicles (EVs) originated from GBM cell lines (U87-MG and LN229) and the significance of EVs in response to chemotherapy in GBM. We first characterised EVs and detected that U87-MG cells release many EVs compared to LN229 cells. Interestingly, TMZ was found to be led to increases in HSF-1, Hsp90, Hsp70, Hsp60 and Hsp27 expression in GBM cells and their EV contents, which these increases are related to therapeutic resistance. What is more, in studies showing which signalling pathways might be associated with these increases, it was observed that TMZ triggered the expression of RAD51 and MDM2 genes in cells and EV contents. More strikingly, we discover a correlation between EV and parental cells in regard of mRNA and protein level in both cell lines as a result of TMZ treatment. Therefore, this data suggest of EVs in the treatment of GBM may have potential biomarkers that can be used to investigate the treatment response.