EGFRvIII overexpression causes loss of neural stem cells phenotype

Abstract

Abstract It is now accepted that the formation of EGFRvIII, a mutated variant of EGFR, may occur early in the tumorigenesis of glioblastoma. Furthermore, it is speculated that glioblastoma may originate from neural stem cells (NSCs), and EGFRvIII itself is considered a marker of cancer stem cells. Therefore, we decided to test the hypothesis that EGFRvIII alteration can occur as the first one in NSC. We created a model of iNSc showing constitutive and induced expression of EGFRvIII. After a series of analyses, we found that EGFRvIII contributed to the loss of SOX2 and nestin - markers of NSCs in both tested models. Interestingly, however, with constitutive expression of EGFRvIII, a senescence phenomenon was observed, while expression induced by low concentrations of doxycycline increased the rate of cell proliferation. Moreover, we observed senescence in the case of high constitutive EGFRvIII expression. Thus, the results suggest that NSCs may not be the origin of glioblastoma cells, and the other cells simultaneously expressing GFAP and SOX2 should be considered the origin of glioblastoma.