Hypoxia-Inducible Factors Regulate Tumorigenic Capacity of Glioma Stem Cells

Zhizhong Li; 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

doi:10.1016/j.ccr.2009.03.018

Hypoxia-Inducible Factors Regulate Tumorigenic Capacity of Glioma Stem Cells

Zhizhong Li
, 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

Duke University Medical Center
Cleveland Clinic Foundation

Research output: Contribution to journal › Article › peer-review

1203 Citations (Scopus)

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 HIF2α and multiple HIF-regulated genes are preferentially expressed in GSCs in comparison to non-stem tumor cells and normal neural progenitors. In tumor specimens, HIF2α 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 HIF2α might represent a promising target for antiglioblastoma therapies.

Original language	English
Pages (from-to)	501-513
Number of pages	13
Journal	Cancer Cell
Volume	15
Issue number	6
DOIs	https://doi.org/10.1016/j.ccr.2009.03.018
Publication status	Published - 2 Jun 2009
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

CELLCYCLE
STEMCELL

Access to Document

10.1016/j.ccr.2009.03.018

Cite this

@article{17b6a0cee52e4424a3a8498169228f44,

title = "Hypoxia-Inducible Factors Regulate Tumorigenic Capacity of Glioma Stem Cells",

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 HIF2α and multiple HIF-regulated genes are preferentially expressed in GSCs in comparison to non-stem tumor cells and normal neural progenitors. In tumor specimens, HIF2α 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 HIF2α might represent a promising target for antiglioblastoma therapies.",

keywords = "CELLCYCLE, STEMCELL",

author = "Zhizhong Li and Shideng Bao and Qiulian Wu and Hui Wang and Christine Eyler and Sith Sathornsumetee and Qing Shi and Yiting Cao and Justin Lathia and McLendon, \{Roger E.\} and Hjelmeland, \{Anita B.\} and Rich, \{Jeremy N.\}",

year = "2009",

month = jun,

day = "2",

doi = "10.1016/j.ccr.2009.03.018",

language = "English",

volume = "15",

pages = "501--513",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - Hypoxia-Inducible Factors Regulate Tumorigenic Capacity of Glioma Stem Cells

AU - Li, Zhizhong

AU - Bao, Shideng

AU - Wu, Qiulian

AU - Wang, Hui

AU - Eyler, Christine

AU - Sathornsumetee, Sith

AU - Shi, Qing

AU - Cao, Yiting

AU - Lathia, Justin

AU - McLendon, Roger E.

AU - Hjelmeland, Anita B.

AU - Rich, Jeremy N.

PY - 2009/6/2

Y1 - 2009/6/2

N2 - 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 HIF2α and multiple HIF-regulated genes are preferentially expressed in GSCs in comparison to non-stem tumor cells and normal neural progenitors. In tumor specimens, HIF2α 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 HIF2α might represent a promising target for antiglioblastoma therapies.

AB - 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 HIF2α and multiple HIF-regulated genes are preferentially expressed in GSCs in comparison to non-stem tumor cells and normal neural progenitors. In tumor specimens, HIF2α 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 HIF2α might represent a promising target for antiglioblastoma therapies.

KW - CELLCYCLE

KW - STEMCELL

UR - https://www.scopus.com/pages/publications/65749106405

U2 - 10.1016/j.ccr.2009.03.018

DO - 10.1016/j.ccr.2009.03.018

M3 - Article

C2 - 19477429

AN - SCOPUS:65749106405

SN - 1535-6108

VL - 15

SP - 501

EP - 513

JO - Cancer Cell

JF - Cancer Cell

IS - 6

ER -

Hypoxia-Inducible Factors Regulate Tumorigenic Capacity of Glioma Stem Cells

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this