Inhibition of Human Prostate Cancer Growth and Prevention of Metastasis Development by Antiangiogenic Activities of Pigment Epithelium-Derived Factor

Background: Human prostate mortality is associated with tumor invasion and metastasis. In this study, we examined the consequences of overexpression of pigment epithelium-derived factor (PEDF) on both prostate cancer primary tumor growth and metastasis development. Methods: In vivo, the prostate cancer cells DU145 with overexpression of PEDF were injected s.c. into SCID mice. The tumor volume (mm 3 ) was measured by applying the formula [volume = 0.52 × (width) 2 × (length)] for approximating the volume of a spheroid, and lung metastases are evaluated using India ink staining. Intratumoral microvessel density (MVD) was detected by immunohistochemistry using mouse anti-human CD31 monoclonal antibody. Human microvessel endothelial cells (HMVEC) tube formation was assayed in vitro. Secreted VEGF was determined by ELISA. Results: The growth of implanted tumor was significantly reduced in sizes, and the lung metastases were also completely inhibited. Compared to control, MVD decreased significantly in the mice transfected with PEDF [(31 ± 3.25) versus (14.25 ± 3.40) (p < 0.01)]. Furthermore, PEDF overexpression also greatly inhibited tube formation in vitro, and decreased production of VEGF in DU145 cells. Conclusions: It was suggested that the effects of PEDF on primary tumor growth and lung metastasis appear associated with inhibition of angiogenic tumor response. PEDF-mediated inhibition of prostate cancer growth and metastases could thus have a major impact on existing therapies for prostate cancer.