Dedifferentiation of patient‐derived glioblastoma multiforme cell lines results in a cancer stem cell‐like state with mitogen‐independent growth

Journal of Cellular and Molecular Medicine

Inan Olmez¹  Wangzhen Shen¹  Hayes McDonald² 

[1] Department of Neurology, Vanderbilt University, Nashville, TN, USA;Department of Biochemistry, Vanderbilt University, Nashville, TN, USA

关键词: glioblastoma multiforme;    cancer stem cells;    salinomycin;    epidermal growth factor receptor;    Oct4;    Nanog;    Sox2;    EphB4;   

DOI  :  10.1111/jcmm.12479

来源: Wiley

【 摘 要 】

Abstract

Emerging evidence shows that glioblastoma multiforme (GBM) originates from cancer stem cells (CSCs). Characterization of CSC-specific signalling pathways would help identify new therapeutic targets and perhaps lead to the development of more efficient therapies selectively targeting CSCs. Here; we successfully dedifferentiated two patient-derived GBM cell lines into CSC-like cells (induced glioma stem cells, iGSCs) 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, iGSCs formed large neurospheres even in the absence of exogenous mitogens; they exhibited significant sensitivity to salinomycin and chemoresistance to temozolomide. Further characterization of iGSCs revealed induction of NOTCH1 and Wnt/β-catenin signalling and expression of CD133, CD44 and ALDH1A1. Our results indicate that iGSCs 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.

【 授权许可】

CC BY   
© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.