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M. B. Crosby, K. Liu, W. Gao, H. Yang, C. E. Hamill, H. E. Grossniklaus; Rise of Serum VEGF in a Murine Model of Uveal Melanoma Is a Predictor of Hepatic Micrometastasis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):57. doi: https://doi.org/.
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Uveal and choroidal melanoma are rare, but up to 40% of patients die within 5 years, usually due to hepatic micrometastasis. Uveal melanomas secrete VEGF that can stimulate tumor blood vessel growth and enhance metastatic potential. We and others have previously shown that melanoma cell lines secrete VEGF. The inhibition of VEGF may prevent or slow the metastatic potential of uveal melanoma. It would be beneficial to be able to detect VEGF levels in the serum of patients with uveal melanoma and correlate this to the potential for metastases or even the presence of difficult to detect micrometastases.
We analyze the serum of C57Bl/6 mice inoculated with uveal melanomas at days 4, 7, 14 and 21 post inoculation for VEGF levels by ELISA (R&D Systems). Additionally we look at the severity and number of hepatic micrometastases and correlate this with the serum VEGF levels noted and the degree of VEGF staining in the livers.
We report that VEGF serum levels rise soon after inoculation of C57Bl/6 mouse eyes with the uveal melanoma cell line. On days 4 and 7 there was a statistically significant (p < 0.01) increase in VEGF levels in the serum of mice inoculated with the uveal melanoma cell line compared with PBS inoculated controls. These levels rose to an average of 37.1 and 10.0 pg/mL respectively compared with a basal level of less than 5pg/mL in the control mice. This level fluctuated, but remained elevated at 21 days post-inoculation before sacrifice up to an average of 18.7 pg/mL compared with less than 5pg/mL in the control mice (p < 0.05). VEGF staining of livers was graded from 0 to 3+. Only one liver was noted to have 2+ staining and this correlated with the highest individual serum VEGF level of 27.8 pg/mL at 21 days.
These data indicate that serum VEGF may be a marker for possible hepatic micrometastases. Clinically, a more sensitive VEGF assay may allow physicians to determine the potential or possibility of metastasis at the time of diagnosis aiding in treatment and prognosis. VEGF inhibition concurrent with uveal melanoma treatment may prevent or slow the metastatic potential of this aggressive tumor and prolong survival.
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