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dc.contributor.authorWang, Jianen_US
dc.contributor.authorSvendsen, Agneteen_US
dc.contributor.authorKmiecik, Justynaen_US
dc.contributor.authorImmervoll, Heikeen_US
dc.contributor.authorSkaftnesmo, Kai Oveen_US
dc.contributor.authorPlanagumà, Jesúsen_US
dc.contributor.authorReed, Rolf K.en_US
dc.contributor.authorBjerkvig, Rolfen_US
dc.contributor.authorMiletic, Hrvojeen_US
dc.contributor.authorEnger, Per Øyvinden_US
dc.contributor.authorRygh, Cecilie Brekkeen_US
dc.contributor.authorChekenya, Marthaen_US
dc.date.accessioned2012-02-21T14:32:50Z
dc.date.available2012-02-21T14:32:50Z
dc.date.issued2011-07-29eng
dc.PublishedPLoS ONE 6(7): e23062en
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/1956/5634
dc.description.abstractAberrant expression of the progenitor marker Neuron-glia 2 (NG2/CSPG4) or melanoma proteoglycan on cancer cells and angiogenic vasculature is associated with an aggressive disease course in several malignancies including glioblastoma multiforme (GBM) and melanoma. Thus, we investigated the mechanism of NG2 mediated malignant progression and its potential as a therapeutic target in clinically relevant GBM and melanoma animal models. Xenografting NG2 overexpressing GBM cell lines resulted in increased growth rate, angiogenesis and vascular permeability compared to control, NG2 negative tumours. The effect of abrogating NG2 function was investigated after intracerebral delivery of lentivirally encoded shRNAs targeting NG2 in patient GBM xenografts as well as in established subcutaneous A375 melanoma tumours. NG2 knockdown reduced melanoma proliferation and increased apoptosis and necrosis. Targeting NG2 in two heterogeneous GBM xenografts significantly reduced tumour growth and oedema levels, angiogenesis and normalised vascular function. Vascular normalisation resulted in increased tumour invasion and decreased apoptosis and necrosis. We conclude that NG2 promotes tumour progression by multiple mechanisms and represents an amenable target for cancer molecular therapy.en_US
dc.language.isoengeng
dc.publisherPLoS Computational Biologyeng
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/eng
dc.titleTargeting the NG2/CSPG4 Proteoglycan Retards Tumour Growth and Angiogenesis in Preclinical Models of GBM and Melanomaen_US
dc.typePeer reviewed
dc.typeJournal article
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2011 Wang et al.
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0023062
dc.subject.nsiVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762eng


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