PMID- 11426944 OWN - NLM STAT- MEDLINE DCOM- 20011214 LR - 20181130 IS - 0014-4827 (Print) IS - 0014-4827 (Linking) VI - 267 IP - 2 DP - 2001 Jul 15 TI - HGF/SF induces mesothelial cell migration and proliferation by autocrine and paracrine pathways. PG - 258-66 AB - Mesothelial repair differs from that of other epithelial-like surfaces as healing does not occur solely by centripetal in-growth of cells as a sheet from the wound margins. Mesothelial cells lose their cell-cell junctions, divide, and adopt a fibroblast-like morphology while scattering across and covering the wound surface. These features are consistent with a cellular response to hepatocyte growth factor/scatter factor (HGF/SF). In this study, we examined the ability of mesothelial cells to secrete HGF/SF and investigated its possible role as an autocrine regulator of mesothelial cell motility and proliferation. We found that human primary mesothelial cells expressed HGF/SF mRNA and secreted active HGF/SF into conditioned medium as determined by ELISA and in a scattering bioassay. These cells also expressed the HGF/SF receptor, Met, as shown by RT-PCR and by Western blot analysis and immunofluorescence. Incubation of mesothelial cells with neutralizing antibodies to HGF/SF decreased cell migration to 25% of controls, whereas addition of HGF/SF disrupted cell-cell junctions and induced scattering and enhanced mesothelial cell migration. Furthermore, HGF/SF showed a small but significant mitogenic effect on all mesothelial cell lines examined. In conclusion, HGF/SF is produced by mesothelial cells and induces both motility and proliferation of these cells. These data are consistent with HGF/SF playing an autocrine role in mesothelial healing. CI - Copyright 2001 Academic Press. FAU - Warn, R AU - Warn R AD - School of Biology, University of East Anglia, Norwich, NR4 7TJ, United Kingdom. FAU - Harvey, P AU - Harvey P FAU - Warn, A AU - Warn A FAU - Foley-Comer, A AU - Foley-Comer A FAU - Heldin, P AU - Heldin P FAU - Versnel, M AU - Versnel M FAU - Arakaki, N AU - Arakaki N FAU - Daikuhara, Y AU - Daikuhara Y FAU - Laurent, G J AU - Laurent GJ FAU - Herrick, S E AU - Herrick SE FAU - Mutsaers, S E AU - Mutsaers SE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Antineoplastic Agents) RN - 6032D45BEM (Suramin) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - Antineoplastic Agents/pharmacology MH - Autocrine Communication/*physiology MH - Cell Division/physiology MH - Cell Movement/*physiology MH - Cells, Cultured MH - Epithelium/drug effects/metabolism/*physiology MH - Hepatocyte Growth Factor/genetics/*metabolism/pharmacology MH - Humans MH - Immunohistochemistry MH - Paracrine Communication/*physiology MH - Proto-Oncogene Proteins c-met/genetics/*metabolism MH - Suramin/pharmacology EDAT- 2001/06/28 10:00 MHDA- 2002/01/05 10:01 CRDT- 2001/06/28 10:00 PHST- 2001/06/28 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/06/28 10:00 [entrez] AID - S0014-4827(01)95240-1 [pii] AID - 10.1006/excr.2001.5240 [doi] PST - ppublish SO - Exp Cell Res. 2001 Jul 15;267(2):258-66. doi: 10.1006/excr.2001.5240.