Journal
CANCER CELL
Volume 18, Issue 6, Pages 655-668Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2010.10.023
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Funding
- Red Tematica de Investigacion Cooperative en Enfermedades Cardiovasculares (RECAVA, ISCIII)
- European Research Council [ERC 205819]
- Instituto Carlos III [FIS PI070648]
- AICR [06-349]
- Cellex Foundation
- AECC
- ICREA Funding Source: Custom
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Glioma-initiating cells (GICs), also called glioma stem cells, are responsible for tumor initiation, relapse, and therapeutic resistance. Here, we show that TGF-beta inhibitors, currently under clinical development, target the GIG compartment in human glioblastoma (GBM) patients. Using patient-derived specimens, we have determined the gene responses to TGF-beta 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-beta pathway decreases the CD44(high)/Id1(high) GIG 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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