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

Yi Hsien Chen, Lucy D.Agostino McGowan, Patrick J. Cimino, Sonika Dahiya, Jeffrey R. Leonard, Da Yong Lee, David H. Gutmann

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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. Inaddition, 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.

Original languageEnglish
Pages (from-to)1899-1912
Number of pages14
JournalCell Reports
Volume10
Issue number11
DOIs
StatePublished - Mar 24 2015

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