PMID- 9546344 OWN - NLM STAT- MEDLINE DCOM- 19980428 LR - 20211203 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 152 IP - 4 DP - 1998 Apr TI - Regulation of uveal melanoma interconverted phenotype by hepatocyte growth factor/scatter factor (HGF/SF). PG - 855-63 AB - Human uveal melanoma disseminates initially and preferentially to the liver. This study describes the relationship between the expression of the c-met proto-oncogene (receptor for hepatocyte growth factor/scatter factor (HGF/SF)) in interconverted uveal melanoma cells (co-expressing vimentin and keratin intermediate filaments) and the regulation of their motogenic response to HGF/SF, a key step in local invasion and targeted dissemination to the liver. Expression of c-met in uveal melanoma cell lines correlates with both the appearance of an interconverted phenotype and invasive ability (measured in vitro). Using chemotactic checkerboard analysis, the greatest motogenic response to HGF/SF was achieved by invasive, interconverted, c-met-positive uveal melanoma cells. C-met was observed histologically in a uveal melanoma containing interconverted cells but was absent in a tumor composed of non-interconverted cells (vimentin positive/keratin negative). The c-met ligand, HGF/SF, although not expressed by uveal melanoma cell lines, was localized in tissue sections of primary uveal melanomas and metastatic melanoma to the liver. In the primary tumor, staining for HGF/SF was most intense at the level of the choriocapillaris, a finding that is significant because 1) highly remodeled neovascular loops and networks, which appear in tumors likely to disseminate, can be traced to the choriocapillaris and the draining vortex veins and 2) HGF/SF plays a role in tumor angiogenesis. Foci of metastatic melanoma to the liver stain diffusely for HGF/SF. Regulation of the uveal melanoma interconverted phenotype by HGF/SF may play an important role in the dissemination of this tumor. FAU - Hendrix, M J AU - Hendrix MJ AD - Department of Anatomy and Cell Biology, Iowa Cancer Center, The University of Iowa College of Medicine, Iowa City 52242-1109, USA. mary-hendrix@uiowa.edu FAU - Seftor, E A AU - Seftor EA FAU - Seftor, R E AU - Seftor RE FAU - Kirschmann, D A AU - Kirschmann DA FAU - Gardner, L M AU - Gardner LM FAU - Boldt, H C AU - Boldt HC FAU - Meyer, M AU - Meyer M FAU - Pe'er, J AU - Pe'er J FAU - Folberg, R AU - Folberg R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - 0 (Vimentin) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 68238-35-7 (Keratins) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - Blotting, Northern MH - Cell Movement/drug effects MH - Hepatocyte Growth Factor/metabolism/pharmacology/*physiology MH - Humans MH - Immunohistochemistry MH - Keratins/metabolism MH - Liver Neoplasms/diagnosis/metabolism/secondary MH - Melanoma/*metabolism/pathology MH - Microscopy, Confocal MH - Models, Biological MH - Prognosis MH - Proto-Oncogene Mas MH - Proto-Oncogene Proteins c-met/metabolism MH - Tumor Cells, Cultured MH - Uveal Neoplasms/*metabolism/pathology MH - Vimentin/metabolism PMC - PMC1858259 EDAT- 1998/04/18 00:00 MHDA- 1998/04/18 00:01 PMCR- 1998/10/01 CRDT- 1998/04/18 00:00 PHST- 1998/04/18 00:00 [pubmed] PHST- 1998/04/18 00:01 [medline] PHST- 1998/04/18 00:00 [entrez] PHST- 1998/10/01 00:00 [pmc-release] PST - ppublish SO - Am J Pathol. 1998 Apr;152(4):855-63.