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

被引：459

作者：

Penuelas, Silvia ^{[1
,4
]}

Anido, Judit ^{[1
,4
]}

Prieto-Sanchez, Rosa M. ^{[1
,4
]}

Folch, Gerard ^{[1
,4
]}

Barba, Ignasi ^{[2
]}

Cuartas, Isabel ^{[1
,4
]}

Garcia-Dorado, David ^{[2
]}

Poca, M. Antonia ^{[3
]}

Sahuquillo, Juan ^{[3
,5
]}

Baselga, Jose ^{[1
,4
,5
]}

Seoane, Joan ^{[1
,4
,5
,6
]}

机构：

[1] Vall DHebron Univ Hosp, Res Inst, Med Oncol Program, Barcelona 08035, Spain

[2] Vall DHebron Univ Hosp, Res Inst, Cardiovasc Program, Barcelona 08035, Spain

[3] Vall DHebron Univ Hosp, Res Inst, Neurosurg Program, Barcelona 08035, Spain

[4] Vall DHebron Inst Oncol, Barcelona 08035, Spain

[5] Autonomous Univ Barcelona, E-08035 Barcelona, Spain

[6] ICREA, Barcelona 08010, Spain

来源：

CANCER CELL | 2009年 / 15卷 / 04期

基金：

欧洲研究理事会;

关键词：

CANCER STEM-CELLS; LEUKEMIA-INHIBITORY FACTOR; GROWTH-FACTOR-BETA; NERVOUS-SYSTEM; DIFFERENTIATION; IDENTIFICATION; SPECIFICITY; POPULATION; PRECURSORS; GENETICS;

D O I：

10.1016/j.ccr.2009.02.011

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

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.

引用

页码：315 / 327

页数：13

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