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S. Champagne, S. Landreville, J. Gagné, S. Leclerc, A. Rousseau, S. Guérin, C. Salesse; Characterization of a Human Uveal Melanocyte Cell Line Generated From the Choroid of a Normal Donor With Properties Typical of Agressive Uveal Melanoma Cell Lines. Invest. Ophthalmol. Vis. Sci. 2008;49(13):78. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Uveal melanoma is the most frequent primary intraocular tumor in the adult population. The metastatic ability of uveal melanoma is particularly elevated as over 50% of the patients with this type of cancer will also develop metastases to the liver. The exact molecular events involved in the formation of the tumor and the metastatic progression of uveal melanoma still remain unclear. The aim of this study was to characterize a spontaneously generated cell line isolated from the uvea of a normal donor with properties typical of aggressive uveal melanoma cell lines.
The MS215 cell line has been isolated and cultured exactly as performed for normal human uveal melanocytes. The phenotype of the MS215 cell line was observed at different passages by optical microscopy. FACS analyses were performed to measure the expression of known markers of uveal melanocytes and epithelial cells as well as several integrin subunits. Their karyotype has been determined as well as their doubling time.
The MS215 cells have an epitheliod-like phenotype and could sustain up to 18 passages without senescence which contrasts with the fibroblast-like phenotype and the low number of passages (4-5) that normal uveal melanocytes can sustain. However, MS215 cells express HMB-45, a well known marker of uveal melanocytes. They also express cytokeratins 8/18 which is consistent with their epithelioid-like phenotype. In addition, the doubling time of this cell line (20.5 h) is ~4-times faster than that of normal uveal melanocytes (more than 78 h). Moreover, this cell line shows a strong expression (as revealed by FACS analyses) and a high promoter activity (as determined by transient transfections) of the alpha 4 integrin subunit whereas normal uveal melanocytes do not express this integrin subunit.
The abnormal karyotype, the short doubling time, the expression of the alpha 4 integrin subunit and the epitheloid-like phenotype of these cell lines are typical of highly invasive uveal melanoma cell lines rather than normal uveal melanocytes. Given that there was no sign for the presence melanoma in the choroid of this normal donor, it can be hypothesized that these cell lines originate from microtumors that were present in the choroid of this patient.
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