Bergen Open Research Archive

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

Bergen Open Research Archive

Show simple item record Svendsen, Agnete Verhoeff, Joost J. C. Immervoll, Heike Brøgger, Jan C. Kmiecik, Justyna Poli, Aurélie Netland, Inger A. Planagumà, Jesús Torsvik, Anja Sakariassen, Per Øystein Bjerkvig, Rolf Enger, Per Øyvind Tronstad, Karl Johan 2011-11-21T10:41:20Z 2011-11-21T10:41:20Z 2011-08-24
dc.identifier.citation Acta Neuropathologica 122(4): 495-510 en
dc.identifier.issn 0001-6322
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 en
dc.publisher Springer en
dc.rights ©The Author(s) 2011 en
dc.rights.uri en
dc.subject Radiation resistance en
dc.subject DNA damage en
dc.subject Glioblastoma en
dc.title Expression of the progenitor marker NG2/CSPG4 predicts poor survival and resistance to ionising radiation in glioblastoma en
dc.type Peer reviewed en
dc.type Journal article en
dc.subject.nsi VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762 en
dc.type.version publishedVersion en

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