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

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-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.

• Authors: 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
• Journal: Cancer cell (Cancer Cell) Vol. 15 Issue 4 Pg. 315-27 (Apr 07 2009) ISSN: 1878-3686 [Electronic] United States
• PMID: 19345330 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• LIF protein, human
• Leukemia Inhibitory Factor
• STAT Transcription Factors
• Smad3 Protein
• Transforming Growth Factor beta
• Transforming Growth Factor beta2
• JAK1 protein, human
• Janus Kinase 1

Topics

• Animals
• Brain Neoplasms (genetics, metabolism, pathology)
• Cell Differentiation
• Cells, Cultured
• Glioblastoma (genetics, metabolism, pathology)
• Humans
• Janus Kinase 1 (genetics, metabolism)
• Leukemia Inhibitory Factor (genetics, metabolism)
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Neurons (cytology, metabolism)
• Promoter Regions, Genetic
• STAT Transcription Factors (genetics, metabolism)
• Signal Transduction
• Smad3 Protein (genetics, metabolism)
• Stem Cells (metabolism)
• Transforming Growth Factor beta (genetics, metabolism)
• Transforming Growth Factor beta2 (genetics, metabolism)