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H. Yang, S. Dithmar, H.E. Grossniklaus; Low-dose Angiostatin Decreases Hepatic Micrometastasis in Murine Ocular Melanoma Model . Invest. Ophthalmol. Vis. Sci. 2003;44(13):933.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate the effect of different concentrations of angiostatin on decreasing hepatic micrometastasis from ocular melanoma. Methods: A murine model for posterior compartment (PC) ocular melanoma was created by inoculating the PCs of the right eyes 12-week-old female C57BL6 mice with equal aliquates of B16LS9, Queens or B16F10 tissue culture melanoma cells. The eyes were enucleated at 7 days post-inoculation and the mice were treated IM with either 100µl injections of PBS or human recombinant angiostatin (group 1=0.3µg/µl or group 2=0.1µg/µl) qd for 14 days after enucleation. The mice were sacrificed at 21 days post-inoculation and hepatic micrometastasis were counted. Western analysis was used to detect angiostatin, PEDF and VEGF in the melanoma cell lines. A Matrigel® migration assay was used to detect melanoma cell migration with angiostatin treatment. Results: There was no decrease in micrometastasis compared with controls in group 1, and a significant decrease in micrometastasis in group 2. Angiostatin production by the melanoma cell lines was inversely proportional to PEDF production. There was negligable VEGF expression by the cell lines. The migration assay correlated to angiostatin response. Conclusions: A low dose of angiostatin reduced the number of micrometastasis in our murine PC ocular melanoma model. This effect may be related to increased PEDF in the presence of high dose angiostatin and decreased cell migration with angistatin treatment. This effect is dependent on the cell line tested.
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