Open AccessDedifferentiation of patient‐derived glioblastoma multiforme cell lines results in a cancer stem cell‐like state with mitogen‐independent growth
Author(s) -
Olmez Inan,
Shen Wangzhen,
McDonald Hayes,
Ozpolat Bulent
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12479
Subject(s) - sox2 , homeobox protein nanog , cancer stem cell , wnt signaling pathway , cancer research , neurosphere , temozolomide , stem cell , biology , glioma , u87 , cell culture , cd44 , stem cell marker , transcription factor , cellular differentiation , signal transduction , microbiology and biotechnology , embryonic stem cell , cell , adult stem cell , biochemistry , genetics , induced pluripotent stem cell , gene
Abstract Emerging evidence shows that glioblastoma multiforme ( GBM ) originates from cancer stem cells ( CSC s). Characterization of CSC ‐specific signalling pathways would help identify new therapeutic targets and perhaps lead to the development of more efficient therapies selectively targeting CSC s. Here; we successfully dedifferentiated two patient‐derived GBM cell lines into CSC ‐like cells (induced glioma stem cells, iGSC s) through expression of Oct4, Sox2 and Nanog transcription factors. Transformed cells exhibited significant suppression of epidermal growth factor receptor and its downstream pathways. Compared with parental GBM cells, iGSC s formed large neurospheres even in the absence of exogenous mitogens; they exhibited significant sensitivity to salinomycin and chemoresistance to temozolomide. Further characterization of iGSC s revealed induction of NOTCH 1 and Wnt/β‐catenin signalling and expression of CD 133, CD 44 and ALDH 1A1. Our results indicate that iGSC s may help us understand CSC physiology and lead to development of potential therapeutic interventions aimed at differentiating tumour cells to render them more sensitive to chemotherapy or other standard agents.