Pleiotrophin enhances PDGFB-induced gliomagenesis through increased proliferation of neural progenitor cells.
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.
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, The Rudbeck Laboratory, Uppsala, Sweden.
Lei
L
Zhang
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, The Rudbeck Laboratory, Uppsala, Sweden.|Division of Brain Sciences, Imperial College Faculty of Medicine, London, UK.
Liisi
L
Laaniste
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, The Rudbeck Laboratory, Uppsala, Sweden.|Department of Molecular Biochemistry and Biophysics, Karolinska Institute, Solna, Sweden.
Yiwen
Y
Jiang
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, The Rudbeck Laboratory, Uppsala, Sweden.|Department of Pathology, Uppsala University Hospital, Uppsala, Sweden.
Irina
I
Alafuzoff
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, The Rudbeck Laboratory, Uppsala, Sweden.
Lene
L
Uhrbom
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, The Rudbeck Laboratory, Uppsala, Sweden.
Anna
A
Dimberg
D000818:Animals; D030161:Avian Proteins / Q000235:genetics; D001358:Avian Sarcoma Viruses / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002897:Chromosomes, Human, Pair 7; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008822:Mice, Transgenic; D060787:Neoplasm Grading; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D011991:Receptors, Virus / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D018874:Spheroids, Cellular; D014162:Transfection
D030161:Avian Proteins; D002352:Carrier Proteins; C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016207:Cytokines; D020574:Proto-Oncogene Proteins c-sis; D011991:Receptors, Virus; C088745:Tva receptor; C066845:pleiotrophin; D051057:Proto-Oncogene Proteins c-akt
chromosome 7; glioma; gliomagenesis; pleiotrophin; tumor initiation