Author/Authors :
Alberto and Peٌuelas، نويسنده , , Silvia and Anido، نويسنده , , Judit and Prieto-Sلnchez، نويسنده , , Rosa M. and Folch، نويسنده , , Gerard and Barba، نويسنده , , Ignasi and Cuartas، نويسنده , , Isabel and Garcيa-Dorado، نويسنده , , David and Poca، نويسنده , , M. Antonia and Sahuquillo، نويسنده , , Juan and Baselga، نويسنده , , José B. Seoane، نويسنده , , Joan، نويسنده ,
Abstract :
Summary
-initiating cells (GICs) are responsible for the initiation and recurrence of gliomas. Here, we identify a molecular mechanism that regulates the self-renewal capacity of patient-derived GICs. We show that TGF-β and LIF induce the self-renewal capacity and prevent the differentiation of GICs. TGF-β induces the self-renewal capacity of GICs, but not of normal human neuroprogenitors, through the Smad-dependent induction of LIF and the subsequent activation of the JAK-STAT pathway. The effect of TGF-β and LIF on GICs promotes oncogenesis in vivo. Some human gliomas express high levels of LIF that correlate with high expression of TGF-β2 and neuroprogenitor cell markers. Our results show that TGF-β and LIF have an essential role in the regulation of GICs in human glioblastoma.
