Format

Send to

Choose Destination
Cell Stem Cell. 2014 Aug 7;15(2):185-98. doi: 10.1016/j.stem.2014.04.007. Epub 2014 May 15.

Targeting self-renewal in high-grade brain tumors leads to loss of brain tumor stem cells and prolonged survival.

Author information

1
Helmholtz Young Investigator Group, Normal and Neoplastic CNS Stem Cells, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
2
Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Department of Neurooncology, University Clinic Heidelberg and German Cancer Consortium (DKTK), Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
3
Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
4
Department of Neuroradiology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
5
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
6
Department of Neuropathology, Heidelberg University Hospital, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany.
7
Helmholtz Young Investigator Group, Normal and Neoplastic CNS Stem Cells, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address: l.haikun@dkfz-heidelberg.de.

Abstract

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.

PMID:
24835569
DOI:
10.1016/j.stem.2014.04.007
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center