Author/Authors :
Anido، نويسنده , , Judit and Sلez-Borderيas، نويسنده , , Andrea and Gonzàlez-Juncà، نويسنده , , Alba and Rodَn، نويسنده , , Laura and Folch، نويسنده , , Gerard and Carmona، نويسنده , , Maria A. and Prieto-Sلnchez، نويسنده , , Rosa M. and Barba، نويسنده , , Ignasi and Martيnez-Sلez، نويسنده , , Elena and Prudkin، نويسنده , , Ludmila and Cuartas، نويسنده , , Isabel and Raventَs، نويسنده , , Carolina and Martيnez-Ricarte، نويسنده , , Francisco and Poca، نويسنده , , M. Antonia and Garcيa-Dorado، نويسنده , , David and Lahn، نويسنده , , Michael M. and Yingling، نويسنده , , Jonathan M. and Rodَn، نويسنده , , Jordi and Sahuquillo، نويسنده , , Juan and Baselga، نويسنده , , José B. Seoane، نويسنده , , Joan، نويسنده ,
Abstract :
Summary
-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 CD44high/Id1high 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.
