Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells.
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.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Vascular Endothelial Growth Factor A
- Stem Cells
- Oncology & Carcinogenesis
- Neovascularization, Pathologic
- Neoplastic Stem Cells
- Neoplasm Transplantation
- Mice, Nude
- Mice, Inbred BALB C
- Mice
- Hypoxia-Inducible Factor 1, alpha Subunit
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Vascular Endothelial Growth Factor A
- Stem Cells
- Oncology & Carcinogenesis
- Neovascularization, Pathologic
- Neoplastic Stem Cells
- Neoplasm Transplantation
- Mice, Nude
- Mice, Inbred BALB C
- Mice
- Hypoxia-Inducible Factor 1, alpha Subunit