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 OlmezBulent Ozpolat

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.

References

Mar 11, 1999·Current Opinion in Neurobiology·D D O'Leary, D G Wilkinson
Jun 25, 1999·Mechanisms of Development·A C OatesA W Boyd
Dec 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·D YanL T Williams
Apr 7, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nicole K NorenElena B Pasquale
Apr 15, 2005·Nature·Tannishtha Reya, Hans Clevers
Jul 4, 2006·The American Journal of Pathology·S Ram KumarParkash S Gill
Jan 20, 2007·Circulation Research·Anne LimbourgFlorian P Limbourg
Sep 13, 2007·Molecular and Cellular Biochemistry·Xue-Ping ZhangJing-Yuan Chen
Nov 3, 2007·Genes & Development·Frank B FurnariWebster K Cavenee
Nov 13, 2008·Science Signaling·Michael B MajorRandall T Moon
Mar 10, 2009·Biochemical and Biophysical Research Communications·Matthieu SchoenhalsBernard Klein
May 12, 2009·Cell Stem Cell·Myung Jin SonHoward A Fine
Sep 29, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Sara G M PiccirilloKhalid Shah
Nov 19, 2009·Stem Cells·Jialiang WangBruce A Sullenger
Feb 16, 2011·Cancer Biology & Therapy·Marco RossiAnnette Bakker
Apr 26, 2011·Methods in Molecular Biology·Johan van MeerlooJacqueline Cloos
Nov 16, 2011·Laboratory Investigation; a Journal of Technical Methods and Pathology·Yonghyun KimDo-Hyun Nam
Jun 2, 2012·The Journal of Clinical Investigation·Jaya SangodkarGoutham Narla
Jun 30, 2012·Proceedings of the National Academy of Sciences of the United States of America·Zhao-Qiu WuStephen J Weiss
Nov 10, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Tao ChenZhigang Liu
Oct 12, 2013·Stem Cells·Hyun Jung JunAlain Charest

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Citations

Nov 1, 2015·International Journal of Cancer. Journal International Du Cancer·Matthias SchneiderMarc-Eric Halatsch
May 6, 2016·Frontiers in Surgery·Amy BradshawTinte Itinteang
Sep 3, 2016·Epigenomics·Wallax Augusto Silva FerreiraBárbara do Nascimento Borges
Oct 13, 2016·Frontiers in Surgery·Amy Ruth BradshawTinte Itinteang
Apr 5, 2017·Stem Cells·Pankaj PrasadTapasya Srivastava
Mar 30, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Joachim BischofTimo Burster
Jan 23, 2018·Current Stem Cell Reports·Seamus P CaragherAtique Ahmed
Oct 21, 2017·Journal of Neuro-oncology·Masafumi MiyaiAkira Hara
May 12, 2018·International Journal of Molecular Medicine·Igor BryukhovetskiyYuri Khotimchenko
Oct 26, 2016·International Journal of Oncology·Kirsten HattermannJanka Held-Feindt
Oct 17, 2019·Genes·Dhananjay HuilgolSonali Bhattacharjee
May 26, 2018·Journal of Cellular and Molecular Medicine·Zhen SunXiujie Wang
Oct 9, 2015·American Journal of Physiology. Cell Physiology·Ying-Jie Wang, Meenhard Herlyn
Aug 18, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Inan OlmezBenjamin Purow
Dec 18, 2020·Frontiers in Genetics·Saniya Deshmukh, Supreet Saini
Apr 13, 2021·Cell Adhesion & Migration·Catherine J LibbyAnita B Hjelmeland

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Methods Mentioned

BETA
electrophoresis
ELISA
flow cytometry
FACS
transfection
SMA

Software Mentioned

GraphPad Prism

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