Induction of differentiation inhibits the tumorigenic potential of glioblastoma cancer stem cells

The outcome of the patients with newly diagnosed glioblastoma remains dismal, despite the use of surgery, radiotherapy and adjuvant temozolomide and while new agents like anti-angiogenic agents seem to offer some promise, a new approach is needed. Recent studies suggest that cancer stem cells (CSCs) may play an important role in malignant gliomas invasion and proliferation. Therefore, CSCs became new therapeutical targets, and one of the main experimental therapies which could be used against CSCs is the differentiation therapy.The purpose of this study was to characterize the CSCs isolated from glioblastoma samples, to assess in vivo the tumorigenic potential of these cells and to induct the differentiation of the CSCs. The changes in invasive markers (matrixmetalloproteases-MMPs, cadherins and cathenins) expression were assessed. CSCs exposed to differentiation inductor factors have been inoculated in nude mice and their tumorigenic potential has been evaluated. The stemness biological feature was correlated with increased of MMPs, cadherins, catenin expression and with tumour contra-lateral invasion. The expression of MMPs, cadherins and cadherins decreased after exposure of the CSCs cultures to the differentiation inductor factors. In vivo experiments demonstrated the inhibition of tumorigenic potential of differentiated CSCs cultures.In conclusion, differentiated CSCs showed a decreased expression of invasive markers in vitro and lost their tumorigenic potential in vivo