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Pleiotrophin enhances PDGFB-induced gliomagenesis through increased proliferation of neural progenitor cells
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Imperial Coll, Fac Med, Div Brain Sci, London, England..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Mol Biochem & Biophys, Solna, Sweden..
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
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2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 49, p. 80382-80390Article in journal (Refereed) Published
Abstract [en]

Pleiotrophin (PTN) augments tumor growth by increasing proliferation of tumor cells and promoting vascular abnormalization, but its role in early gliomagenesis has not been evaluated. Through analysis of publically available datasets, we demonstrate that increased PTN mRNA expression is associated with amplification of chromosome 7, identified as one of the earliest steps in glioblastoma development. To elucidate the role of PTN in tumor initiation we employed the RCAS/tv-a model that allows glioma induction by RCAS-virus mediated expression of oncogenes in neural progenitor cells. Intracranial injection of RCAS-PTN did not induce glioma formation when administrated alone, but significantly enhanced RCAS-platelet derived growth factor (PDGF) B-induced gliomagenesis. PTN co-treatment augmented PDGFBinduced Akt activation in neural progenitor cells in vitro, and enhanced neural sphere size associated with increased proliferation. Our data indicates that PTN expression is associated with chromosome 7 gain, and that PTN enhances PDGFB-induced gliomagenesis by stimulating proliferation of neural progenitor cells.

Place, publisher, year, edition, pages
2016. Vol. 7, no 49, p. 80382-80390
Keyword [en]
glioma, pleiotrophin, gliomagenesis, tumor initiation, chromosome 7
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-313533DOI: 10.18632/oncotarget.12983ISI: 000389877500027OAI: oai:DiVA.org:uu-313533DiVA, id: diva2:1070730
Funder
Swedish Cancer Society, CAN 2011/862 CAN 2014/832 CAN 2015/1216Swedish Childhood Cancer Foundation, PR2013-0107 PR2015-0133 NCp2015-0075Swedish Research Council, 2013-3797
Available from: 2017-02-02 Created: 2017-01-20 Last updated: 2017-11-29Bibliographically approved

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Zhang, LeiJiang, YiwenAlafuzoff, IrinaUhrbom, LeneDimberg, Anna
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Science for Life Laboratory, SciLifeLabVascular BiologyDepartment of Immunology, Genetics and PathologyNeuro-OncologyClinical and experimental pathology
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