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

Abstract

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 epitheliumderived 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.

Kallikrein-binding protein inhibits growth of gastric carcinoma by reducing vascular endothelial growth factor production and angiogenesis

“…However, the effect of KBP on the expression and release of VEGF in tumor cells has not been investigated. Recent studies showed that pigment epithelium-derived factor, a member of the same superfamily, suppressed tumor growth by inhibiting VEGF expression in tumor cells (20,21). Therefore, the hypothesis that KBP can regulate VEGF in tumor cells was detected for the first time in the present study.…”

Untitled

“…Y705 phosphorylation IL-6 is a pro-inflammatory cytokine regulated by TLR3 and has been shown to be important for the growth and migration of cancer cells [21][22][23]. It has also been shown to be an activator of a key oncogene, STAT3, known to mediate uncontrolled cell growth in many types of human cancers [24].…”

Antitumor activity of placenta-derived mesenchymal stem cells producing pigment epithelium-derived factor in a mouse melanoma model

“…A number of studies demonstrate that a low level of PEDF is associated with the increased incidence of metastasis and poor malignancy prognosis in various tumors (25). Garcia et al and Abe et al showed that overexpression of PEDF in malignant melanoma cell lines by stable transfection with retrovirus and plasmids, respectively, markedly reduced intratumoral microvessel density as well as primary tumor growth and metastasis (26,27). In our previous study, the potent antitumor activity of adenovirus-mediated PEDF was demonstrated in B16-F10 melanoma.…”