TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma.
Cancer Cell
; 15(4): 315-27, 2009 Apr 07.
Article
em En
| MEDLINE
| ID: mdl-19345330
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Fator de Crescimento Transformador beta
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Glioblastoma
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Fator Inibidor de Leucemia
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Neurônios
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Espanha