Format

Send to

Choose Destination
See comment in PubMed Commons below
Cancer Cell. 2009 Jun 2;15(6):501-13. doi: 10.1016/j.ccr.2009.03.018.

Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells.

Author information

1
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.

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.

PMID:
19477429
PMCID:
PMC2693960
DOI:
10.1016/j.ccr.2009.03.018
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center