Journal article
Regulation of uveal melanoma interconverted phenotype by hepatocyte growth factor/scatter factor (HGF/SF)
The American journal of pathology, Vol.152(4), pp.855-863
04/1998
PMCID: PMC1858259
PMID: 9546344
Abstract
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.
Details
- Title: Subtitle
- Regulation of uveal melanoma interconverted phenotype by hepatocyte growth factor/scatter factor (HGF/SF)
- Creators
- Mary J.C. Hendrix - Department of Anatomy and Cell Biology, Iowa Cancer Center, The University of Iowa College of Medicine, Iowa City 52242-1109, USAElisabeth A Seftor - Department of Anatomy and Cell Biology, Iowa Cancer Center, The University of Iowa College of Medicine, Iowa City 52242-1109, USARichard E B Seftor - Department of Anatomy and Cell Biology, Iowa Cancer Center, The University of Iowa College of Medicine, Iowa City 52242-1109, USADawn A Kirschmann - Department of Anatomy and Cell Biology, Iowa Cancer Center, The University of Iowa College of Medicine, Iowa City 52242-1109, USALynn M Gardner - Department of Anatomy and Cell Biology, Iowa Cancer Center, The University of Iowa College of Medicine, Iowa City 52242-1109, USAH Culver Boldt - Department of Anatomy and Cell Biology, Iowa Cancer Center, The University of Iowa College of Medicine, Iowa City 52242-1109, USAMargaret Meyer - Department of Anatomy and Cell Biology, Iowa Cancer Center, The University of Iowa College of Medicine, Iowa City 52242-1109, USAJacob Pe'er - Department of Anatomy and Cell Biology, Iowa Cancer Center, The University of Iowa College of Medicine, Iowa City 52242-1109, USARobert Folberg - Department of Anatomy and Cell Biology, Iowa Cancer Center, The University of Iowa College of Medicine, Iowa City 52242-1109, USA
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.152(4), pp.855-863
- PMID
- 9546344
- PMCID
- PMC1858259
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Language
- English
- Date published
- 04/1998
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9984083235502771
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