Mouse low-grade gliomas contain cancer stem cells with unique molecular and functional properties

Cell Reports
Yi-Hsien ChenDavid H Gutmann

Abstract

The availability of adult malignant glioma stem cells (GSCs) has provided unprecedented opportunities to identify the mechanisms underlying treatment resistance. Unfortunately, there is a lack of comparable reagents for the study of pediatric low-grade glioma (LGG). Leveraging a neurofibromatosis 1 (Nf1) genetically engineered mouse LGG model, we report the isolation of CD133(+) multi-potent low-grade glioma stem cells (LG-GSCs), which generate glioma-like lesions histologically similar to the parent tumor following injection into immunocompetent hosts. In addition, we demonstrate that these LG-GSCs harbor selective resistance to currently employed conventional and biologically targeted anti-cancer agents, which reflect the acquisition of new targetable signaling pathway abnormalities. Using transcriptomic analysis to identify additional molecular properties, we discovered that mouse and human LG-GSCs harbor high levels of Abcg1 expression critical for protecting against ER-stress-induced mouse LG-GSC apoptosis. Collectively, these findings establish that LGG cancer stem cells have unique molecular and functional properties relevant to brain cancer treatment.

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Citations

Nov 21, 2015·Neoplasia : an International Journal for Oncology Research·Anne C SolgaDavid H Gutmann
Dec 8, 2015·Glia·Suzanne J BakerDavid H Gutmann
Jan 31, 2017·Annual Review of Pathology·Courtney L MonroeDavid H Gutmann
Dec 17, 2017·Journal of Child Neurology·Cynthia J Campen, David H Gutmann
Apr 29, 2018·Journal of Neuroscience Research·Morgan E Freret, David H Gutmann
Mar 18, 2020·The Journal of Experimental Medicine·Xiaoyan ZhanJianghong Man
Mar 17, 2016·Oncotarget·Yi-Hsien ChenDavid H Gutmann
Jun 16, 2016·Oncotarget·Yanzhou YangWai Yee Chan
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Jan 10, 2017·Frontiers in Oncology·Cora A RickerCharles Keller
Nov 17, 2019·Cancer Letters·Francesco AlessandriniPaolo Malatesta
Jun 17, 2021·Neuro-oncology·Till MildeDavid H Gutmann
Oct 9, 2021·Drug Discovery Today·Ting Xiang LimDavid C Reutens

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