期刊
CELL STEM CELL
卷 15, 期 2, 页码 185-198出版社
CELL PRESS
DOI: 10.1016/j.stem.2014.04.007
关键词
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资金
- Helmholtz Association [VH-NG-702]
- Deutsche Forschungsgemeinschaft [LI 2140/1-1]
- Deutsche Krebshilfe [110226]
- Helmholtz Alliance Preclinical Comprehensive Cancer Center (PCCC)
- DKFZ Intramural Grant Program
- DKFZ-Bayer Healthcare Alliance
Cancer stem cells (CSCs) have been suggested as potential therapeutic targets for treating malignant tumors, but the in vivo supporting evidence is still missing. Using a GFP reporter driven by the promoter of the nuclear receptor tailless (Tlx), we demonstrate that Tlx(+) cells in primary brain tumors are mostly quiescent. Lineage tracing demonstrates that single Tlx(+) cells can self-renew and generate Tlx(-) tumor cells in primary tumors, suggesting that they are brain tumor stem cells (BTSCs). After introducing a BTSC-specific knock-out of the Tlx gene in primary mouse tumors, we observed a loss of self-renewal of BTSCs and prolongation of animal survival, accompanied by induction of essential signaling pathways mediating cell-cycle arrest, cell death, and neural differentiation. Our study demonstrates the feasibility of targeting glioblastomas and indicates the suitability of BTSCs as therapeutic targets, thereby supporting the CSC hypothesis.
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