Mouse low-grade gliomas contain cancer stem cells with unique molecular and functional properties.
Mouse low-grade gliomas contain cancer stem cells with unique molecular and functional properties.
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DOI：
10.1016/j.celrep.2015.02.041
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发表时间：
2015-03-24
期刊：
影响因子：
8.8
通讯作者：
Gutmann DH
中科院分区：
文献类型：
--
作者：
Chen YH;McGowan LD;Cimino PJ;Dahiya S;Leonard JR;Lee DY;Gutmann DH
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 transcriptomal analysis to identify additional molecular properties, we discovered that mouse and human LG-GSCs harbor high levels of Abcg1 expression critical for protecting against endoplasmic reticulum (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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