PMID- 10389763 OWN - NLM STAT- MEDLINE DCOM- 19990719 LR - 20190708 IS - 0020-7136 (Print) IS - 0020-7136 (Linking) VI - 82 IP - 2 DP - 1999 Jul 19 TI - 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. PG - 274-81 AB - 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. FAU - Hamasuna, R AU - Hamasuna R AD - Second Department of Pathology, Miyazaki Medical College, Japan. FAU - Kataoka, H AU - Kataoka H FAU - Moriyama, T AU - Moriyama T FAU - Itoh, H AU - Itoh H FAU - Seiki, M AU - Seiki M FAU - Koono, M AU - Koono M LA - eng PT - Journal Article PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (Benzoquinones) RN - 0 (Enzyme Inhibitors) RN - 0 (Lactams, Macrocyclic) RN - 0 (Neoplasm Proteins) RN - 0 (Quinones) RN - 0 (RNA, Messenger) RN - 0 (RNA, Neoplasm) RN - 0 (Recombinant Proteins) RN - 1W306TDA6S (Rifabutin) RN - 62229-50-9 (Epidermal Growth Factor) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 70563-58-5 (herbimycin) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 3.4.24.- (Gelatinases) RN - EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated) RN - EC 3.4.24.- (Metalloendopeptidases) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) SB - IM MH - Benzoquinones MH - Brain Neoplasms/enzymology/genetics/*pathology MH - Disease Progression MH - Enzyme Induction/drug effects MH - Enzyme Inhibitors/pharmacology MH - Epidermal Growth Factor/pharmacology MH - Gelatinases/*biosynthesis/genetics MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Glioblastoma/enzymology/genetics/pathology MH - Glioma/enzymology/genetics/*pathology MH - Hepatocyte Growth Factor/*pharmacology MH - Humans MH - Lactams, Macrocyclic MH - Matrix Metalloproteinase 2 MH - Matrix Metalloproteinases, Membrane-Associated MH - Metalloendopeptidases/*biosynthesis/genetics MH - Neoplasm Invasiveness MH - Neoplasm Proteins/*biosynthesis/genetics MH - Protein-Tyrosine Kinases/antagonists & inhibitors MH - Quinones/pharmacology MH - RNA, Messenger/biosynthesis/genetics MH - RNA, Neoplasm/biosynthesis/genetics MH - Recombinant Proteins/pharmacology MH - Rifabutin/analogs & derivatives MH - Signal Transduction/drug effects MH - Stimulation, Chemical MH - Tumor Cells, Cultured EDAT- 1999/07/02 10:00 MHDA- 2000/06/20 09:00 CRDT- 1999/07/02 10:00 PHST- 1999/07/02 10:00 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1999/07/02 10:00 [entrez] AID - 10.1002/(SICI)1097-0215(19990719)82:2<274::AID-IJC19>3.0.CO;2-2 [pii] AID - 10.1002/(sici)1097-0215(19990719)82:2<274::aid-ijc19>3.0.co;2-2 [doi] PST - ppublish SO - Int J Cancer. 1999 Jul 19;82(2):274-81. doi: 10.1002/(sici)1097-0215(19990719)82:2<274::aid-ijc19>3.0.co;2-2.