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

Silvia Peñuelas, Judit Anido, Rosa M. Prieto-Sánchez, Gerard Folch, Ignasi Barba, Isabel Cuartas, David García-Dorado, M. Antonia Poca, Juan Sahuquillo, Jose Baselga, Joan Seoane

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340 Citations (Scopus)

Abstract

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-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. © 2009 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)315-327
JournalCancer Cell
Volume15
Issue number4
DOIs
Publication statusPublished - 7 Apr 2009

Keywords

  • CELLCYCLE
  • STEMCELL

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    Peñuelas, S., Anido, J., Prieto-Sánchez, R. M., Folch, G., Barba, I., Cuartas, I., García-Dorado, D., Poca, M. A., Sahuquillo, J., Baselga, J., & Seoane, J. (2009). TGF-β Increases Glioma-Initiating Cell Self-Renewal through the Induction of LIF in Human Glioblastoma. Cancer Cell, 15(4), 315-327. https://doi.org/10.1016/j.ccr.2009.02.011