NOVH increases MMP3 expression and cell migration in glioblastoma cells via a PDGFR-alpha-dependent mechanism.
Nephroblastoma overexpressed gene (NOV) is highly expressed in the nervous system. We investigated its biological activity by expressing the human NOV gene (NOVH) in a human glioblastoma cell line that is negative for NOVH and by analyzing four clones with different levels of NOVH expression. There was no difference in cell proliferation between the NOVH-expressing cell lines, but there was increased cell adhesion and migration that correlated with increasing NOVH expression. Gene expression profiling was used to investigate the mechanisms by which NOVH expression regulated cell activity. We identified two induced genes in NOVH-expressing cells that are involved in cell migration: matrix metalloprotease (MMP)3 and platelet-derived growth factor receptor (PDGFR)-alpha. Our studies show that PDGFR-alpha induced MMP3 gene expression and increased cell proliferation and cell migration upon stimulation by platelet-derived growth factor (PDGF)-AA. We also show that the induction of MMP3 in cells expressing NOVH is potentiated by either cell density, serum, or PDGF-BB. Thus, expression of NOVH in glioblastoma cells triggers a cascade of gene expression resulting in increased cell adhesion and migration.
D000077214:Becaplermin; D001932:Brain Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D055513:Connective Tissue Growth Factor; D005786:Gene Expression Regulation; D005909:Glioblastoma / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000235:genetics; D008954:Models, Biological; D055514:Nephroblastoma Overexpressed Protein; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
C526317:CCN2 protein, human; C526319:CCN3 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055514:Nephroblastoma Overexpressed Protein; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D055513:Connective Tissue Growth Factor; D000077214:Becaplermin; D020796:Receptor, Platelet-Derived Growth Factor alpha; D019278:Matrix Metalloproteinase 3