Journal article
Biologic determinants of uveal melanoma metastatic phenotype : Role of intermediate filaments as predictive markers
Laboratory investigation, Vol.78(2), pp.153-163
1998
PMID: 9484713
Abstract
The long-range goal of our research is to develop intervention strategies based on newly discovered biologic mechanisms responsible for the invasive dissemination of metastatic uveal melanoma. To accomplish this goal, we have focused on the biologic relevance of novel marker proteins contributing to the uveal melanoma metastatic phenotype. The expression of vimentin intermediate filaments (IFs), a mesenchymal marker, is typical of melanomas, whereas carcinomas typically express keratin IFs, which are markers for epithelia. Thus, cells that coexpress both IFs are regarded as "interconverted" in that they display both mesenchymal and epithelial phenotypes. Although the biologic functions of IFs have remained enigmatic, there is substantial support to suggest that the significance of vimentin/keratin coexpression is linked with poor patient outcome in cutaneous melanoma. Our data demonstrate that human uveal melanoma cell lines (isolated from primary choroidal or ciliary body melanomas and from foci of metastatic uveal melanoma to the liver), which contain predominant populations of cells that coexpress vimentin/keratins 8 and 18 (keratins 8,18) IFs, were 6-fold more invasive through collagenous extracellular matrices in vitro, compared with uveal melanoma cells expressing vimentin only, and were 8- to 13-fold more invasive than normal uveal melanocytes. Colocalization of vimentin/keratins 8,18 in cell cultures was corroborated by immunohistochemistry in histologic sections of tumors from which the cell lines were derived. Minor populations of these cells also coexpressed keratins 13 and 17. Experimental down-regulation of the predominant keratins 8,18 in the interconverted cells, using 16-mer antisense oligonucleotides, resulted in a significant decrease in the migratory ability of the cells-similar to levels achieved by cells positive only for vimentin. These findings provide justification for additional studies of the association between coexpression of IFs vimentin/keratins 8,18 and uveal melanoma metastasis.
Details
- Title: Subtitle
- Biologic determinants of uveal melanoma metastatic phenotype : Role of intermediate filaments as predictive markers
- Creators
- M. J. C HENDRIX - Department of Anatomy and Cell Biology, The University of Iowa College of Medicine, Iowa City, Iowa, United StatesE. A SEFTOR - Department of Anatomy and Cell Biology, The University of Iowa College of Medicine, Iowa City, Iowa, United StatesR. E. B SEFTOR - Department of Anatomy and Cell Biology, The University of Iowa College of Medicine, Iowa City, Iowa, United StatesL. M GARDNER - Department of Ophthalmology and Visual Sciences, The University of Iowa College of Medicine, Iowa City, Iowa, United StatesH. C BOLDT - Department of Ophthalmology and Visual Sciences, The University of Iowa College of Medicine, Iowa City, Iowa, United StatesM MEYER - Department of Ophthalmology and Visual Sciences, The University of Iowa College of Medicine, Iowa City, Iowa, United StatesJ PE'ER - Department of Ophthalmology, Hadassah University Hospital, Jerusalem, IsraelR FOLBERG - Iowa Cancer Center, The University of Iowa College of Medicine, Iowa City, Iowa, United States
- Resource Type
- Journal article
- Publication Details
- Laboratory investigation, Vol.78(2), pp.153-163
- Publisher
- Nature Publishing
- PMID
- 9484713
- ISSN
- 0023-6837
- eISSN
- 1530-0307
- Language
- English
- Date published
- 1998
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9984083808502771
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