RRC ID 39370
Author Hamasuna R, Kataoka H, Moriyama T, Itoh H, Seiki M, Koono M.
Title Regulation of matrix metalloproteinase-2 (MMP-2) by hepatocyte growth factor/scatter factor (HGF/SF) in human glioma cells: HGF/SF enhances MMP-2 expression and activation accompanying up-regulation of membrane type-1 MMP.
Journal Int. J. Cancer
Abstract Hepatocyte growth factor/scatter factor (HGF/SF) contributes to the malignant progression of human gliomas. We investigated the effect of HGF/SF on matrix metalloproteinase-2 (MMP-2), membrane type 1 matrix metalloproteinase (MT1-MMP) and tissue inhibitors of metalloproteinases (TIMPs), expressions of c-Met/HGF receptor-positive human glioblastoma cells. Treatment of U251 human glioblastoma cells with HGF/SF resulted in enhanced secretion of MMP-2 with an increased level of the active form. This was accompanied by enhanced expression (2.5-fold) of mRNA specific for MMP-2. The stimulatory effect of HGF/SF on MMP-2 expression did not occur in the presence of herbimycin A, a protein tyrosine kinase inhibitor. MT1 -MMP, a cell-surface activator of proMMP-2, was also up-regulated by HGF/SF in a dose-dependent manner. By contrast, the level of TIMP- 1 mRNAs was not altered significantly and that of TIMP-2 was reduced mildly by the HGF/SF treatment, suggesting that HGF/SF may eventually modulate a balance between MMP-2 and TIMPs in favor of the proteinase activity in the glioma cell microenvironment. HGF/SF also stimulated MMP-2 expression of other glioblastoma cell lines. Since glioblastomas frequently co-express HGF/SF and its receptor, our results suggest that HGF/SF might contribute to the invasiveness of glioblastoma cells through autocrine induction of MMP-2 expression and activation.
Volume 82(2)
Pages 274-81
Published 1999-7-19
DOI 10.1002/(sici)1097-0215(19990719)82:2<274::aid-ijc19>3.0.co;2-2
PII 10.1002/(SICI)1097-0215(19990719)82:2<274::AID-IJC19>3.0.CO;2-2
PMID 10389763
MeSH Benzoquinones Brain Neoplasms / enzymology Brain Neoplasms / genetics Brain Neoplasms / pathology* Disease Progression Enzyme Induction / drug effects Enzyme Inhibitors / pharmacology Epidermal Growth Factor / pharmacology Gelatinases / biosynthesis* Gelatinases / genetics Gene Expression Regulation, Neoplastic / drug effects* Glioblastoma / enzymology Glioblastoma / genetics Glioblastoma / pathology Glioma / enzymology Glioma / genetics Glioma / pathology* Hepatocyte Growth Factor / pharmacology* Humans Lactams, Macrocyclic Matrix Metalloproteinase 2 Matrix Metalloproteinases, Membrane-Associated Metalloendopeptidases / biosynthesis* Metalloendopeptidases / genetics Neoplasm Invasiveness Neoplasm Proteins / biosynthesis* Neoplasm Proteins / genetics Protein-Tyrosine Kinases / antagonists & inhibitors Quinones / pharmacology RNA, Messenger / biosynthesis RNA, Messenger / genetics RNA, Neoplasm / biosynthesis RNA, Neoplasm / genetics Recombinant Proteins / pharmacology Rifabutin / analogs & derivatives Signal Transduction / drug effects Stimulation, Chemical Tumor Cells, Cultured
IF 7.36
Times Cited 56
Human and Animal Cells