Dedifferentiated cells obtained from glioblastoma cell lines are an easy and robust model for mesenchymal glioblastoma stem cells studies

Glioblastoma is an aggressive brain tumor with a poor prognosis. Glioblastoma Stem Cells (GSC) are involved in glioblastoma resistance and relapse. Effective glioblastoma treatment must include GSC targeting strat-egy. Robust and well defined in vitro GSC models are required for new therapies evaluation. In this study, we exten-sively characterized 4 GSC models obtained by dedifferentiation of commercially available glioblastoma cell lines and compared them to 2 established patient derived GSC lines (Brain Tumor Initiating Cells). Dedifferentiated cells formed gliospheres, typical for GSC, with self-renewal ability. Gene expression and protein analysis revealed an in-creased expression of several stemness associated markers such as A2B5, integrin a6, Nestin, SOX2 and NANOG. Cells were oriented toward a mesenchymal GSC phenotype as shown by elevated levels of mesenchymal and EMT related markers (CD44, FN1, integrin a5). Dedifferentiated GSC were similar to BTIC in terms of size and heteroge-neity. The characterization study also revealed that CXCR4 pathway was activated by dedifferentiation, emphasiz-ing its role as a potential therapeutic target. The expression of resistance-associated markers and the phenotypic diversity of the 4 GSC models obtained by dedifferentiation make them relevant to challenge future GSC targeting therapies.