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Inhibition of Xenografted Human Melanoma Growth and Prevention of Metastasis Development by Dual Antiangiogenic/Antitumor Activities of Pigment Epithelium-Derived Factor

¹ Project on Damage, Repair and Tissue Engineering CIEMAT and Fundación M. Botin, Madrid, Spain; ² Department of Biochemistry, Universidad Autónoma de Madrid-Instituto de Investigaciones Biomédicas CSIC-UAM, Madrid, Spain; ³ Department of Molecular and Cellular Biology and Dermatology, Huffington Center on Aging, Baylor College of Medicine, Houston, Texas; and ⁴ Northwestern University Medical School, Department of Urology, Chicago, Illinois

Human melanoma mortality is associated with the growth of metastasis in selected organs including the lungs, liver, and brain. In this study, we examined the consequences of overexpression of pigment epithelium-derived factor (PEDF), a neurotrophic factor and potent angiogenesis inhibitor, on both melanoma primary tumor growth and metastasis development. PEDF overexpression by melanoma cells greatly inhibited subcutaneous tumor formation and completely prevented lung and liver metastasis in immunocompromised mice after tail vein injection of metastatic human melanoma cell lines. Whereas the effects of PEDF on primary tumor xenografts appear mostly associated with inhibition of the angiogenic tumor response, abrogation of melanoma metastasis appears to depend on direct PEDF effects on both migration and survival of melanoma cells. PEDF-mediated inhibition of melanoma metastases could thus have a major impact on existing therapies for melanoma.

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