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TGF-beta Increases Glioma-Initiating Cell Self-Renewal through the Induction of LIF in Human Glioblastoma

  作者 Penuelas, S; Anido, J; Prieto-Sanchez, RM; Folch, G; Barba, I; Cuartas, I; Garcia-Dorado, D; Poca, MA; Sahuquillo, J; Baselga, J; Seoane, J  
  选自 期刊  Cancer Cell;  卷期  2009年15-4;  页码  315-327  
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[摘要]Glioma-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-beta and LIF induce the self-renewal capacity and prevent the differentiation of GICs. TGF-beta 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-beta and LIF on GICs promotes oncogenesis in vivo. Some human gliomas express high levels of LIF that correlate with high expression of TGF-beta 2 and neuroprogenitor cell markers. Our results show that TGF-beta and LIF have an essential role in the regulation of GICs in human glioblastoma.

 
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