PMID- 11027427 OWN - NLM STAT- MEDLINE DCOM- 20001207 LR - 20181113 IS - 0007-0920 (Print) IS - 1532-1827 (Electronic) IS - 0007-0920 (Linking) VI - 83 IP - 9 DP - 2000 Nov TI - Hepatocyte growth factor/scatter factor enhances the invasion of mesothelioma cell lines and the expression of matrix metalloproteinases. PG - 1147-53 AB - Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional factor involved both in development and tissue repair, as well as pathological processes such as cancer and metastasis. It has been identified in vivo in many types of tumours together with its tyrosine kinase receptor, Met. We show here that exogenous HGF/SF acts as a strong chemoattractant for human mesothelioma cell lines. The factor also enhanced cell adhesion to and invasion into Matrigel. The mesothelioma cell lines synthesized a panel of matrix metalloproteinases critical for tumour progression such as MMP-1, 2, 3, 9 and membrane-bound MT1-MMP. HGF/SF stimulated the expression of MMP-1, 9 and MT1-MMP and had a slight effect on expression of the MMP inhibitor TIMP-1 but not TIMP-2. However, there was no simple correlation between the levels of MMPs and TIMPs of the cell lines and their different invasion properties or between HGF/SF stimulatory effects on MMP expression and invasion. In addition, effects of protease inhibitors on invasion suggested that serine proteases were also expressed in human mesothelioma cell lines and were involved in HGF/SF-induced invasion. The results show a predominant role for HGF/SF in mesothelioma cell invasion, stimulating simultaneously adhesion, motility, invasion and regulation of MMP and TIMP levels. CI - Copyright 2000 Cancer Research Campaign. FAU - Harvey, P AU - Harvey P AD - School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, UK. FAU - Clark, I M AU - Clark IM FAU - Jaurand, M C AU - Jaurand MC FAU - Warn, R M AU - Warn RM FAU - Edwards, D R AU - Edwards DR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 RN - 0 (Drug Combinations) RN - 0 (Laminin) RN - 0 (Proteoglycans) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 119978-18-6 (matrigel) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 9007-34-5 (Collagen) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM MH - Cell Adhesion/drug effects MH - Cell Movement/*drug effects MH - Collagen MH - Dose-Response Relationship, Drug MH - Drug Combinations MH - Hepatocyte Growth Factor/*pharmacology MH - Humans MH - Laminin MH - Matrix Metalloproteinase 1/drug effects/metabolism MH - Matrix Metalloproteinase 2/drug effects/metabolism MH - Matrix Metalloproteinase 9/drug effects/metabolism MH - Matrix Metalloproteinases/*drug effects/metabolism MH - Mesothelioma/*enzymology/pathology MH - Neoplasm Invasiveness MH - Proteoglycans MH - Tissue Inhibitor of Metalloproteinase-1/drug effects/metabolism MH - Tumor Cells, Cultured PMC - PMC2363594 EDAT- 2000/10/12 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/10/12 11:00 PHST- 2000/10/12 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/10/12 11:00 [entrez] AID - S0007092000914459 [pii] AID - 10.1054/bjoc.2000.1445 [doi] PST - ppublish SO - Br J Cancer. 2000 Nov;83(9):1147-53. doi: 10.1054/bjoc.2000.1445.