Purchase this article with an account.
J.–C.A. Marshall, A. Nantel, P.L. Blanco, J. Ash, M.N. Burnier, Jr.; Transcriptional Profiling of Circulating Malignant Cells Isolated From an Animal Model of Uveal Melanoma . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2235.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Uveal melanoma is the most common intraocular tumor in adults and is exclusively disseminated via a haematogenous route in order to form metastasis. The aim of this study is to measure the transcriptional profiles of human uveal melanoma cells isolated and cultured from the intraocular primary tumor, circulating malignant cells and metastasic locations.
Human single–spotted 19k microarrays and universal human reference RNA were used to measure the differences between cultured cells isolated from various locations in an immunosuppressed rabbit model of uveal melanoma. Cells were isolated at the time of sacrifice from intraocular, peripheral blood and metastasis. RNA was then extracted from each sample and subjected to transcriptional profiling analysis. Results were compared to the transcriptional profiles previously obtained from the original 92.1 cell line injected into the eye of the rabbits.
Statistical analysis using an ANOVA cut off of 0.05 revealed 3123 transcripts that were modulated between the re–cultured cells from each location and the original 92.1 cell line. 207 of those transcripts had at least a two fold increase or decrease. Included in the transcripts of interest that were up regulated in the circulating malignant cells were Septin 7, Alpha Kinase 3, and Insulin receptor substrate 2. Melanoma specific markers such as Melan A were included in the group of transcripts that were down regulated.
For the first time we describe proteins that are significantly up or down regulated between primary, circulating malignant cells and metastasis in uveal melanoma. These changes included transcription factors, ribosomal proteins, and melanoma specific markers. Moreover, cells that were re–cultured after isolation from blood maintained these significant changes. These changes allow us to investigate the expression patterns that uveal melanoma cells may require to survive through circulation until the time of implantation at a distant organ. Future work will investigate the role of these factors in the survival of cells in circulation and their role in metastasis.
This PDF is available to Subscribers Only