title: Deficiency of the protein-tyrosine phosphatase DEP-1/PTPRJ promotes matrix metalloproteinase-9 expression in meningioma cells.
abstract: Brain-invasive growth of a subset of meningiomas is associated with less favorable prognosis. The molecular mechanisms causing invasiveness are only partially understood, however, the expression of matrix metalloproteinases (MMPs) has been identified as a contributing factor. We have previously found that loss of density enhanced phosphatase-1 (DEP-1, also designated PTPRJ), a transmembrane protein-tyrosine phosphatase, promotes meningioma cell motility and invasive growth in an orthotopic xenotransplantation model. We have now analyzed potential alterations of the expression of genes involved in motility control, caused by DEP-1 loss in meningioma cell lines. DEP-1 depleted cells exhibited increased expression of mRNA encoding MMP-9, and the growth factors EGF and FGF-2. The increase of MMP-9 expression in DEP-1 depleted cells was also readily detectable at the protein level by zymography. MMP-9 upregulation was sensitive to chemical inhibitors of growth factor signal transduction. Conversely, MMP-9 mRNA levels could be stimulated with growth factors (e.g. EGF) and inflammatory cytokines (e.g. TNFα). Increase of MMP-9 expression by DEP-1 depletion, or growth factor/cytokine stimulation qualitatively correlated with increased invasiveness in vitro scored as transmigration through matrigel-coated membranes. The studies suggest induction of MMP-9 expression promoted by DEP-1 deficiency, or potentially by growth factors and inflammatory cytokines, as a mechanism contributing to meningioma brain invasiveness.
authors: Institute of Molecular Cell Biology, CMB, Jena University Hospital, Hans-Knöll-Strasse 2, 07745, Jena, Germany.
authors: Astrid
authors: A
authors: Petermann
authors: Yvonn
authors: Y
authors: Stampnik
authors: Yan
authors: Y
authors: Cui
authors: Helen
authors: H
authors: Morrison
authors: Doreen
authors: D
authors: Pachow
authors: Nadine
authors: N
authors: Kliese
authors: Christian
authors: C
authors: Mawrin
authors: Frank-D
authors: FD
authors: Böhmer
mesh_terms: D000704:Analysis of Variance; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D016518:Neurofibromatosis 2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000172:deficiency / Q000235:genetics; D014162:Transfection
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; C486288:PTPRJ protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9