Involvement of macrophage migration inhibitory factor (MIF) in the mechanism of tumor cell growth

Background: Macrophage migration inhibitory factor (MIF) was recently redis covered as a cytokine, pituitary hormone, and gIucocorticoid-induced immuno modulator. MIF is constitutively expressed in various cells and enhances pr oduction of inflammatory cytokines such as tumor necrosis factor-alpha, int erleukin-l, and interferon gamma. Recently it was reported that MIF mRNA wa s overexpressed in prostatic tumors, which suggests that MIF is a protein i nvolved in tumor cell growth beyond inflammatory and immune responses. Materials and Methods: We examined the expression of MIE; in the murine col on carcinoma cell line colon 26 by Western and Northern blot analyses and i mmunohistochemistry. Next, we investigated the effects of transforming grow th factor (TGF) beta, basic fibroblast growth factor (b-FGF), and platelet- derived growth factor (PDGF) on the expression of MIF mRNA. Furthermore, we examined whether MIF is involved in tumor cell proliferation, using an MIE : anti-sense plasmid transfection technique. Results: We demonstrated that MIF protein and its mRNA were highly expresse d in colon 26 cells, using Western and Northern blot analyses, respectively . By immunohistochemical analysis, we found that MIF was localized largely in the cytoplasm of the tumor cells. In response to TGF-beta, b-FGF, and PD GF, MIF mRNA expression Was significantly up-regulated. Following this, we transfected the cells with an anti-sense MIF plasmid; which revealed that t his treatment induced significant suppression of cell proliferation. Conclusion: Although MIF plays multifunctional roles in a broad spectrum of pathophysiological states, little has been done to investigate the role of this protein in association with tumor growth. The current results suggest the possibility that MIF induces tumor cell growth in concert with other g rowth factors, which encouraged us to investigate a novel approach for tumo r therapy using an anti-MIF antibody and an MIF anti-sense plasmid transfec tion technique.