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.
Pubmed ID: 21156287 RIS Download
Mesh terms: Animals | Antigens, CD44 | Brain Neoplasms | Glioblastoma | Humans | Inhibitor of Differentiation Protein 1 | Inhibitor of Differentiation Proteins | Mice | Mice, SCID | Neoplasm Proteins | Receptors, Transforming Growth Factor beta | Xenograft Model Antitumor Assays
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