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Cancer Cell. 2009 Apr 7;15(4):315-27. doi: 10.1016/j.ccr.2009.02.011.

TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma.

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Medical Oncology Program, Vall d'Hebron University Hospital Research Institute, Barcelona, Spain.


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-beta2 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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