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Cancer Cell. 2010 Dec 14;18(6):655-68. doi: 10.1016/j.ccr.2010.10.023.

TGF-β Receptor Inhibitors Target the CD44(high)/Id1(high) Glioma-Initiating Cell Population in Human Glioblastoma.

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1
Vall d'Hebron Institute of Oncology, Barcelona, Spain.

Abstract

Glioma-initiating cells (GICs), also called glioma stem cells, are responsible for tumor initiation, relapse, and therapeutic resistance. Here, we show that TGF-β inhibitors, currently under clinical development, target the GIC compartment in human glioblastoma (GBM) patients. Using patient-derived specimens, we have determined the gene responses to TGF-β inhibition, which include inhibitors of DNA-binding protein (Id)-1 and -3 transcription factors. We have identified a cell population enriched for GICs that expresses high levels of CD44 and Id1 and tend to be located in a perivascular niche. The inhibition of the TGF-β pathway decreases the CD44(high)/Id1(high) GIC population through the repression of Id1 and Id3 levels, therefore inhibiting the capacity of cells to initiate tumors. High CD44 and Id1 levels confer poor prognosis in GBM patients.

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PMID:
21156287
DOI:
10.1016/j.ccr.2010.10.023
[Indexed for MEDLINE]
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