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

Judit Anido, Andrea Sáez-Borderías, Alba Gonzàlez-Juncà, Laura Rodón, Gerard Folch, Maria A. Carmona, Rosa M. Prieto-Sánchez, Ignasi Barba, Elena Martínez-Sáez, Ludmila Prudkin, Isabel Cuartas, Carolina Raventós, Francisco Martínez-Ricarte, M. Antonia Poca, David García-Dorado, Michael M. Lahn, Jonathan M. Yingling, Jordi Rodón, Juan Sahuquillo, José BaselgaJoan Seoane

Research output: Contribution to journalArticleResearchpeer-review

396 Citations (Scopus)

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. © 2010 Elsevier Inc.
Original languageEnglish
Pages (from-to)655-668
JournalCancer Cell
Volume18
Issue number6
DOIs
Publication statusPublished - 14 Dec 2010

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