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Expression of the progenitor marker NG2/CSPG4 predicts poor survival and resistance to ionising radiation in glioblastoma

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dc.contributor.author Svendsen, Agnete eng
dc.contributor.author Verhoeff, Joost J. C. eng
dc.contributor.author Immervoll, Heike eng
dc.contributor.author Brøgger, Jan C. eng
dc.contributor.author Kmiecik, Justyna eng
dc.contributor.author Poli, Aurélie eng
dc.contributor.author Netland, Inger A. eng
dc.contributor.author Planagumà, Jesús eng
dc.contributor.author Torsvik, Anja eng
dc.contributor.author Sakariassen, Per Øystein eng
dc.contributor.author Bjerkvig, Rolf eng
dc.contributor.author Enger, Per Øyvind eng
dc.contributor.author Tronstad, Karl Johan eng
dc.date.accessioned 2011-11-21T10:41:20Z
dc.date.available 2011-11-21T10:41:20Z
dc.date.issued 2011-08-24 eng
dc.identifier.citation Acta Neuropathologica 122(4): 495-510 en
dc.identifier.issn 0001-6322 eng
dc.identifier.uri http://hdl.handle.net/1956/5203
dc.description There are 22 authors. Only a few of them have been given author entries in addition to the Collaboration en
dc.description.abstract Glioblastoma (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.iso eng eng
dc.publisher Springer eng
dc.rights.uri http://www.springer.com/open+access/open+choice?SGWID=0-40359-0-0-0 eng
dc.subject Radiation resistance eng
dc.subject DNA damage eng
dc.subject Glioblastoma eng
dc.title Expression of the progenitor marker NG2/CSPG4 predicts poor survival and resistance to ionising radiation in glioblastoma eng
dc.type Peer reviewed eng
dc.type Journal article eng
dc.subject.nsi VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762 eng
dc.rights.holder ©The Author(s) 2011
dc.type.version publishedVersion eng
bora.peerreviewed Peer reviewed eng
bibo.doi http://dx.doi.org/10.1007/s00401-011-0867-2 eng
dc.identifier.doi http://dx.doi.org/10.1007/s00401-011-0867-2


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