The significance of tumor cells-derived MFG-E8 in tumor growth of angiosarcoma.

BACKGROUND:Previous studies have indicated that MFG-E8 enhances tumor cell survival, invasion and angiogenesis. However, the role of MFG-E8 in angiosarcoma (AS) has not been clarified. OBJECTIVE:Objective was to elucidate the mechanism of the regulation by MFG-E8 in AS and the association between MFG-E8 and clinicopathological features of AS. METHODS:The effects of the depletion of MFG-E8 by siRNA on tube formation, migration and proliferation in murine AS cells were examined. The effect of administration of anti-MFG-E8 antibody (Ab) on tumor growth of AS in mice was examined. The associations of MFG-E8 expression and clinicopathological features of human AS were assessed. RESULTS:The expressions of MFG-E8 in murine and human AS cells were significantly higher than those in melanoma cells, macrophages and endothelial cells. Depletion of MFG-E8 in murine AS cells by siRNA significantly inhibited the formation of capillary-like structures and migration, but not proliferation. Administration of anti-MFG-E8 Ab significantly inhibited tumor growth and decreased the number of tumor-associated macrophages (TAMs) in AS tumors. Tumor size and the number of TAMs in human AS with high expression of MFG-E8 were significantly increased compared to those of AS with low expression of MFG-E8. Progression-free survival and overall survival time of the patients of AS with high expression of MFG-E8 were significantly shorter than those of AS with low expression of MFG-E8. CONCLUSIONS:AS-derived MFG-E8 might enhance tumor growth via angiogenesis and the induction of TAMs in autocrine/paracrine manner, and administration of anti-MFG-E8 Ab could be a therapeutic potential for AS.

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