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S. Wang, D. M. Albert, A. Nekhra, C. M. Sorenson, N. Sheibani; Suppression of Thrombospondin-1 Expression During Uveal Melanoma Progression and Its Utilization as Potential Therapeutic. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6388.
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To determine whether expression of thrombospondin-1 (TSP1), an endogenous inhibitor of angiogenesis, is down-regulated during progression of uveal melanoma and if administration of TSP1 and/or its antiangiogenic peptide attenuate tumor growth.
Tyr-tag transgenic mice were used for evaluation of TSP1 expression during tumor progression using immunohistological methods. The therapeutic potential of TSP1 on tumor progression was evaluated by either crossing Tyr-tag mice to a transgenic mouse that over expresses TSP1 in the eye, or by administration of TSP1 peptide mimetics with known antiangiogenic, antitumor activity. Tumor areas were measured in histological sections using Optima software.
Tyr-tag tumors from 3-week-old mice showed significant TSP1 expression which was dramatically down-regulated in tumors from 12-week-old mice. Furthermore, the development and progression of tumor was significantly delayed in Tyr-tag/TSP1 transgenic mice or Tyr-tag mice receiving TSP1 peptide (100 mg/Kg/day).
TSP1 expression is decreased with angiogenic switch during progression of uveal melanoma. TSP1 and/or its antiangiogenic peptides are effective in attenuation of tumor growth. Therefore, antiangiogenic therapy may be beneficial for treatment of uveal melanoma.
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