• Yi-Hsien Chen, Lucy D'Agostino McGowan, Patrick J Cimino, Sonika Dahiya, Jeffrey R Leonard, Da Yong Lee, and David H Gutmann.
• Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
• Cell Rep. 2015 Mar 24;10(11):1899-912.

AbstractThe 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.Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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