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A. Neekhra, S. R. Darjatmoko, C. M. Sorenson, D. M. Albert, N. Sheibani; Attenuation of Uveal Melanoma Growth in Eyes of Mice Expressing Increased Levels of Thrombospondin-1. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5952.
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Thrombospondin-1 (TSP1) is an endogenous inhibitor of angiogenesis whose expression is down regulated in many tumors as they gain an angiogenic phenotype. However, its role during uveal melanoma development and progression is not well understood. Here we investigated the development and progression of uveal melanomas in transgenic Tyr-Tag mice which express increased levels of TSP1 in their eye.
The transgenic mice that over-express TSP1 in their lens were previously described. These mice were crossed with a line of Tyr-Tag mice, which are known to produce intraocular pigmented tumors resembling uveal melanoma. This resulted in generation of transgenic mice that express Tyr-Tag and TSP1 (Tyr-Tag/TSP1). The histopathological evaluations were performed with eyes obtained from eight-week-old wild type, Tyr-Tag, TSP1-transgenic, and Tyr-Tag/TSP1 transgenic mice. The tumor areas were measured in histological sections using Optima software.
We observed a significant delay in the development of tumors in Tyr-Tag/TSP1 mice compared to Tyr-Tag mice. The average size of uveal melanoma tumors in Tyr-Tag/TSP1 mice were about 1/10th the size of tumors in Tyr-Tag mice. Histologically the tumor cells were similar in the two groups. No tumors were detected in wild type or TSP1 transgenic mice.
The down-regulation of TSP1 appears to contribute to the development and progression of uveal melanomas. The administration of TSP1 or its antiangiogenic peptides may be effective in blocking uveal melanoma growth by limiting their angiogenic property.
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