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A hypoxic niche reg...
A hypoxic niche regulates glioblastoma stem cells through hypoxia inducible factor 2 alpha
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- Seidel, Sascha (author)
- Institute of Neuropathology, Justus Liebig University, 35392 Giessen, Germany
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- Garvalov, Boyan K. (author)
- Institute of Neuropathology, Justus Liebig University, 35392 Giessen, Germany
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- Wirta, Valtteri (author)
- KTH,Genteknologi
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- von Stechow, Louise (author)
- Edinger Institute, Goethe University Medical School, 60528 Frankfurt am Main, German
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- Schaenzer, Anne (author)
- Institute of Neuropathology, Justus Liebig University, 35392 Giessen, Germany
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- Meletis, Konstantinos (author)
- Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden
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- Wolter, Marietta (author)
- Department of Neuropathology, Heinrich Heine University, Du ̈ sseldorf, 40225 Germany
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- Sommerlad, Daniel (author)
- Edinger Institute, Goethe University Medical School, 60528 Frankfurt am Main, German
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- Henze, Anne-Theres (author)
- Institute of Neuropathology, Justus Liebig University, 35392 Giessen, Germany
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- Nister, Monica (author)
- Karolinska Institutet
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- Reifenberger, Guido (author)
- Department of Neuropathology, Heinrich Heine University, Du ̈ sseldorf, 40225 Germany
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- Lundeberg, Joakim (author)
- KTH,Genteknologi
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- Frisen, Jonas (author)
- Karolinska Institutet
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- Acker, Till (author)
- Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden
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(creator_code:org_t)
- 2010-04-05
- 2010
- English.
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 133, s. 983-995
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Abstract
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- Glioma growth and progression depend on a specialized subpopulation of tumour cells, termed tumour stem cells. Thus, tumour stem cells represent a critical therapeutic target, but the molecular mechanisms that regulate them are poorly understood. Hypoxia plays a key role in tumour progression and in this study we provide evidence that the hypoxic tumour microenvironment also controls tumour stem cells. We define a detailed molecular signature of tumour stem cell genes, which are overexpressed by tumour cells in vascular and perinecrotic/hypoxic niches. Mechanistically, we show that hypoxia plays a key role in the regulation of the tumour stem cell phenotype through hypoxia-inducible factor 2 alpha and subsequent induction of specific tumour stem cell signature genes, including mastermind-like protein 3 (Notch pathway), nuclear factor of activated T cells 2 (calcineurin pathway) and aspartate beta-hydroxylase domain-containing protein 2. Notably, a number of these genes belong to pathways regulating the stem cell phenotype. Consistently, tumour stem cell signature genes are overexpressed in newly formed gliomas and are associated with worse clinical prognosis. We propose that tumour stem cells are maintained within a hypoxic niche, providing a functional link between the well-established role of hypoxia in stem cell and tumour biology. The identification of molecular regulators of tumour stem cells in the hypoxic niche points to specific signalling mechanisms that may be used to target the glioblastoma stem cell population.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- tumour stem cells
- side population
- glioblastoma
- hypoxia
- hypoxia inducible factor
- hypoxic niche
- Tumour biology
- Tumörbiologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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Brain
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- By the author/editor
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Seidel, Sascha
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Garvalov, Boyan ...
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Wirta, Valtteri
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von Stechow, Lou ...
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Schaenzer, Anne
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Meletis, Konstan ...
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Wolter, Marietta
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Sommerlad, Danie ...
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Henze, Anne-Ther ...
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Nister, Monica
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Reifenberger, Gu ...
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Lundeberg, Joaki ...
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Frisen, Jonas
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Acker, Till
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Brain
- By the university
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Royal Institute of Technology
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Karolinska Institutet