Constitutive overexpression of pigment epithelium-derived factor inhibition of ocular melanoma growth and metastasis.

Pigment epithelium-derived factor (PEDF) is known to be an angiogenesis suppressor and to have antitumor effects. This study investigates whether constitutive overexpression of PEDF inhibits the growth and hepatic micrometastasis of ocular melanoma. Real-time RT-PCR was used to detect endogenous PEDF expression in human uveal melanoma cell lines and mouse melanoma cells. A lentiviral vector containing a mouse PEDF expression sequence was constructed and transduced into mouse melanoma cells in vitro. Transgene expression was assessed by Western blot analysis. Angiogenesis and transendothelial migration assays were performed in constitutively stable PEDF-overexpressing cells and transduced lentiviral vector control cells. The size and microvessel density of the ocular tumor and the number of hepatic micrometastasis were compared between the mice inoculated with PEDF-overexpressing tumor cells and those mice with the control cell line. Four human uveal melanoma and three mouse melanoma cell lines were found to express PEDF mRNA. Endogenous overexpressing PEDF melanoma cells lost the ability to migrate and form tubes in vitro. In the animal experiment, the size of the ocular melanoma and the number of hepatic micrometastasis were decreased and microvessel density was also reduced in mice inoculated with constitutively overexpressing PEDF melanoma cells. Lentivirus-mediated gene transfer of PEDF decreased the growth of ocular melanoma and its hepatic micrometastasis in a mouse ocular melanoma model. Dual antitumor/antiangiogenic activities of PEDF suggest that PEDF gene therapy may be considered an approach for the treatment of ocular melanoma.