Macrophages have the potential to re-programing tumor cells in the tumor microenvironments. Thus we investigated anti-cancer effects of M1-polarized macrophages by lipopolysaccharide (LPS) on the physiological properties of human prostate cancer PC-3 cells. To identify communications with immune cells and tumor cells, we performed in-direct way by using conditioned-media (CM) and analyzed tumor properties via quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and western blot and flow cytometry. CM of M1-polarized macrophages induced apoptotic cell death in PC-3 cells, and it surprisingly suppressed tumor parameters including epithelial to mesenchymal transition (EMT), invasion, migration and angiogenesis. EMT specific markers, N-cadherin, snail-1, and TGF β2 were diminished; however, E-cadherin was increased. In addition, migration markers, vimentin and CCL2 were down-regulated, and finally wound healing was also inhibited. Decreased expression of matrix metalloprotein (MMP)-9 and VEGFA might reduce the invasive and angiogenic abilities of PC-3 cells. These results suggested that co-culture with CM of M1-polarized macrophages showed higher anti-cancer effects on PC-3 cells. Thus, therapeutic targeting of macrophages toward PC-3 cells may represent a useful strategy to complement with the secreted molecules of RAW 264.7 cells as inhibitors of metastasis and anti-cancer agents.
Keywords: Human prostate cancer PC-3 cells; epithelial to mesenchymal transition; lipopolysaccharide; murine macrophage RAW 264.7 cells; polarization.
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