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  • Seidel, SaschaInstitute of Neuropathology, Justus Liebig University, 35392 Giessen, Germany (author)

A hypoxic niche regulates glioblastoma stem cells through hypoxia inducible factor 2 alpha

  • Article/chapterEnglish2010

Publisher, publication year, extent ...

  • 2010-04-05
  • Oxford University Press (OUP),2010
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-28237
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-28237URI
  • https://doi.org/10.1093/brain/awq042DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:120359221URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20110119
  • 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 and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Garvalov, Boyan K.Institute of Neuropathology, Justus Liebig University, 35392 Giessen, Germany (author)
  • Wirta, ValtteriKTH,Genteknologi(Swepub:kth)u1u59vht (author)
  • von Stechow, LouiseEdinger Institute, Goethe University Medical School, 60528 Frankfurt am Main, German (author)
  • Schaenzer, AnneInstitute of Neuropathology, Justus Liebig University, 35392 Giessen, Germany (author)
  • Meletis, KonstantinosDepartment of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden (author)
  • Wolter, MariettaDepartment of Neuropathology, Heinrich Heine University, Du ̈ sseldorf, 40225 Germany (author)
  • Sommerlad, DanielEdinger Institute, Goethe University Medical School, 60528 Frankfurt am Main, German (author)
  • Henze, Anne-TheresInstitute of Neuropathology, Justus Liebig University, 35392 Giessen, Germany (author)
  • Nister, MonicaKarolinska Institutet (author)
  • Reifenberger, GuidoDepartment of Neuropathology, Heinrich Heine University, Du ̈ sseldorf, 40225 Germany (author)
  • Lundeberg, JoakimKTH,Genteknologi(Swepub:kth)u1qkn9kw (author)
  • Frisen, JonasKarolinska Institutet (author)
  • Acker, TillDepartment of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden (author)
  • Institute of Neuropathology, Justus Liebig University, 35392 Giessen, GermanyGenteknologi (creator_code:org_t)

Related titles

  • In:Brain: Oxford University Press (OUP)133, s. 983-9950006-89501460-2156

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