Hypoxia-Inducible Factors Regulate Tumorigenic Capacity of Glioma Stem Cells

被引：1272

作者：

Li, Zhizhong ^{[1
]}

Bao, Shicleng ^{[2
,5
]}

Wu, Qiulian ^{[2
,5
]}

Wang, Hui ^{[1
]}

Eyler, Christine ^{[1
,2
]}

Sathornsumetee, Sith ^{[2
]}

Shi, Qing ^{[2
]}

Cao, Yiting ^{[2
]}

Lathia, Justin ^{[2
,5
]}

McLendon, Roger E. ^{[3
]}

Hjelmeland, Anita B. ^{[2
,5
]}

Rich, Jeremy N. ^{[1
,2
,4
,5
]}

机构：

[1] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA

[2] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA

[3] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA

[4] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA

[5] Cleveland Clin, Dept Stem Cell Biol & Regenerat Med, Cleveland, OH 44195 USA

来源：

CANCER CELL | 2009年 / 15卷 / 06期

关键词：

ENDOTHELIAL GROWTH-FACTOR; GENE-EXPRESSION; BRAIN-TUMORS; RADIATION-RESISTANCE; HIF-2-ALPHA PROMOTES; DRUG-RESISTANCE; CANCER; GLIOBLASTOMA; ANGIOGENESIS; CD133;

D O I：

10.1016/j.ccr.2009.03.018

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Glioblastomas are lethal cancers characterized by florid angiogenesis promoted in part by glioma stem cells (GSCs). Because hypoxia regulates angiogenesis, we examined hypoxic responses in GSCs. We now demonstrate that hypoxia-inducible factor HIF2 alpha and multiple HIF-regulated genes are preferentially expressed in GSCs in comparison to non-stem tumor cells and normal neural progenitors. In tumor specimens, HIF2 alpha colocalizes with cancer stem cell markers. Targeting HIFs in GSCs inhibits self-renewal, proliferation, and survival in vitro, and attenuates tumor initiation potential of GSCs in vivo. Analysis of a molecular database reveals that HIF2A expression correlates with poor glioma patient survival. Our results demonstrate that GSCs differentially respond to hypoxia with distinct HIF induction patterns, and HIF2 alpha might represent a promising target for antiglioblastoma therapies.

引用

页码：501 / 513

页数：13

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