| Literature DB >> 19477429 |
Zhizhong Li1, Shideng Bao, Qiulian Wu, Hui Wang, Christine Eyler, Sith Sathornsumetee, Qing Shi, Yiting Cao, Justin Lathia, Roger E McLendon, Anita B Hjelmeland, Jeremy N Rich.
Abstract
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 HIF2alpha and multiple HIF-regulated genes are preferentially expressed in GSCs in comparison to non-stem tumor cells and normal neural progenitors. In tumor specimens, HIF2alpha 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 HIF2alpha might represent a promising target for antiglioblastoma therapies.Entities:
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Year: 2009 PMID： 19477429 PMCID： PMC2693960 DOI： 10.1016/j.ccr.2009.03.018
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743