Pleiotrophin enhances PDGFB-induced gliomagenesis through increased proliferation of neural progenitor cells

// Lei Zhang 1 , Liisi Laaniste 1,2 , Yiwen Jiang 1,3 , Irina Alafuzoff 1,4 , Lene Uhrbom 1 and Anna Dimberg 1 1 Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, The Rudbeck Laboratory, Uppsala, Sweden 2 Division of Brain Sciences, Imperial College Faculty of Medicine, London, UK 3 Department of Molecular Biochemistry and Biophysics, Karolinska Institute, Solna, Sweden 4 Department of Pathology, Uppsala University Hospital, Uppsala, Sweden Correspondence to: Anna Dimberg, email: // Keywords : glioma, pleiotrophin, gliomagenesis, tumor initiation, chromosome 7 Received : October 07, 2016 Accepted : October 11, 2016 Published : October 28, 2016 Abstract 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 PDGFB-induced 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.