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dc.contributor.authorSvendsen, Agneteeng
dc.contributor.authorVerhoeff, Joost J. C.eng
dc.contributor.authorImmervoll, Heikeeng
dc.contributor.authorBrøgger, Jan C.eng
dc.contributor.authorKmiecik, Justynaeng
dc.contributor.authorPoli, Aurélieeng
dc.contributor.authorNetland, Inger A.eng
dc.contributor.authorPlanagumà, Jesúseng
dc.contributor.authorTorsvik, Anjaeng
dc.contributor.authorSakariassen, Per Øysteineng
dc.contributor.authorBjerkvig, Rolfeng
dc.contributor.authorEnger, Per Øyvindeng
dc.contributor.authorTronstad, Karl Johaneng
dc.date.accessioned2011-11-21T10:41:20Z
dc.date.available2011-11-21T10:41:20Z
dc.date.issued2011-08-24eng
dc.identifier.citationActa Neuropathologica 122(4): 495-510en
dc.identifier.issn0001-6322eng
dc.identifier.urihttp://hdl.handle.net/1956/5203
dc.descriptionThere are 22 authors. Only a few of them have been given author entries in addition to the Collaborationen
dc.description.abstractGlioblastoma (GBM) is a highly aggressive brain tumour, where patients respond poorly to radiotherapy and exhibit dismal survival outcomes. The mechanisms of radioresistance are not completely understood. However, cancer cells with an immature stem-like phenotype are hypothesised to play a role in radioresistance. Since the progenitor marker neuron-glial-2 (NG2) has been shown to regulate several aspects of GBM progression in experimental systems, we hypothesised that its expression would influence the survival of GBM patients. Quantification of NG2 expression in 74 GBM biopsies from newly diagnosed and untreated patients revealed that 50% express high NG2 levels on tumour cells and associated vessels, being associated with significantly shorter survival. This effect was independent of age at diagnosis, treatment received and hypermethylation of the O6-methylguanine methyltransferase (MGMT) DNA repair gene promoter. NG2 was frequently co-expressed with nestin and vimentin but rarely with CD133 and the NG2 positive tumour cells harboured genetic aberrations typical for GBM. 2D proteomics of 11 randomly selected biopsies revealed upregulation of an antioxidant, peroxiredoxin-1 (PRDX-1), in the shortest surviving patients. Expression of PRDX-1 was associated with significantly reduced products of oxidative stress. Furthermore, NG2 expressing GBM cells showed resistance to ionising radiation (IR), rapidly recognised DNA damage and effectuated cell cycle checkpoint signalling. PRDX-1 knockdown transiently slowed tumour growth rates and sensitised them to IR in vivo. Our data establish NG2 as an important prognostic factor for GBM patient survival, by mediating resistance to radiotherapy through induction of ROS scavenging enzymes and preferential DNA damage signalling.en
dc.language.isoengeng
dc.publisherSpringereng
dc.rights.urihttp://www.springer.com/open+access/open+choice?SGWID=0-40359-0-0-0eng
dc.subjectRadiation resistanceeng
dc.subjectDNA damageeng
dc.subjectGlioblastomaeng
dc.titleExpression of the progenitor marker NG2/CSPG4 predicts poor survival and resistance to ionising radiation in glioblastomaeng
dc.typePeer reviewedeng
dc.typeJournal articleeng
dc.subject.nsiVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762eng
dc.rights.holder©The Author(s) 2011
dc.type.versionpublishedVersioneng
bora.peerreviewedPeer reviewedeng
bibo.doihttp://dx.doi.org/10.1007/s00401-011-0867-2eng
dc.identifier.doihttp://dx.doi.org/10.1007/s00401-011-0867-2


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