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

Publication ,  Journal Article
Li, Z; Bao, S; Wu, Q; Wang, H; Eyler, C; Sathornsumetee, S; Shi, Q; Cao, Y; Lathia, J; McLendon, RE; Hjelmeland, AB; Rich, JN
Published in: Cancer Cell
June 2, 2009

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

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Published In

Cancer Cell

DOI

EISSN

1878-3686

Publication Date

June 2, 2009

Volume

15

Issue

6

Start / End Page

501 / 513

Location

United States

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

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Li, Z., Bao, S., Wu, Q., Wang, H., Eyler, C., Sathornsumetee, S., … Rich, J. N. (2009). Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell, 15(6), 501–513. https://doi.org/10.1016/j.ccr.2009.03.018
Li, Zhizhong, Shideng Bao, Qiulian Wu, Hui Wang, Christine Eyler, Sith Sathornsumetee, Qing Shi, et al. “Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells.Cancer Cell 15, no. 6 (June 2, 2009): 501–13. https://doi.org/10.1016/j.ccr.2009.03.018.
Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S, et al. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell. 2009 Jun 2;15(6):501–13.
Li, Zhizhong, et al. “Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells.Cancer Cell, vol. 15, no. 6, June 2009, pp. 501–13. Pubmed, doi:10.1016/j.ccr.2009.03.018.
Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S, Shi Q, Cao Y, Lathia J, McLendon RE, Hjelmeland AB, Rich JN. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell. 2009 Jun 2;15(6):501–513.
Journal cover image

Published In

Cancer Cell

DOI

EISSN

1878-3686

Publication Date

June 2, 2009

Volume

15

Issue

6

Start / End Page

501 / 513

Location

United States

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