Regular Article
High Expression of Macrophage Migration Inhibitory Factor in Human Melanoma Cells and Its Role in Tumor Cell Growth and Angiogenesis

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Abstract

Macrophage migration inhibitory factor (MIF) is known to function as a cytokine, hormone, and glucocorticoid-induced immunoregulator. In this study, we reported for the first time that human melanocytes and melanoma cells express MIF mRNA and produce MIF protein. Immunohistochemical analysis demonstrated that MIF was mostly localized in the cytoplasm of melanocytes and G361 cells, a widely available human melanoma cell line. In particular, strong positive staining was observed at the dendrites of these cells. Expression of MIF mRNA and production of MIF protein were much higher in human melanoma cells such as G361, A375, and L32 than in normal cultured melanocytes. To assess the role of MIF overexpression in melanoma cells, G361 cells were transfected with an antisense human MIF plasmid. The results demonstrated that the cell growth rate of the transfected cells was markedly suppressed, suggesting that MIF participates in the mechanism of proliferation of melanoma cells. To further evaluate the function of MIF, we employed the Boyden chamber method to examine the effect on tumor cell migration and found that MIF enhanced the migration of G361 cells in a dose-dependent manner. Furthermore, we administered anti-MIF antibody into tumor (G361 cells in a Millipore chamber)-bearing mice to assess the effect on tumor-associated angiogenesis. The anti-MIF antibody significantly suppressed tumor-induced angiogenesis. Taken together, these results indicated that it is likely that MIF may function as a novel growth factor that stimulates incessant growth and invasion of melanoma concomitant with neovascularization.

References (38)

  • P.R. Gordon et al.

    J. Invest. Dermatol.

    (1989)
  • V.P. Swope et al.

    J. Invest. Dermatol.

    (1991)
  • V.P. Swope et al.

    J. Invest. Dermatol.

    (1994)
  • C.O.C. Zachariae et al.

    J. Invest. Dermatol.

    (1991)
  • A. Matsuda et al.

    Immunol. Lett.

    (1996)
  • H. Suzuki et al.

    Immunol. Lett.

    (1996)
  • H. Schagger et al.

    Anal. Biochem.

    (1987)
  • H. Sugimoto et al.

    FEBS Lett.

    (1996)
  • G. Michel et al.

    FEBS Lett.

    (1992)
  • S. Onodera et al.

    Cytokine

    (1999)
  • T. Shimizu et al.

    J. Invest. Dermatol.

    (1999)
  • K. Meyer-Siegler et al.

    Urology

    (1996)
  • R.A. Mitchell et al.

    J. Biol. Chem.

    (1999)
  • J.G. Morelli et al.

    J. Invest. Dermatol.

    (1993)
  • A. Ramirez-Bosca et al.

    Arch. Dermatol. Res.

    (1992)
  • M. De Kuca et al.

    J. Cell. Biol.

    (1988)
  • A. Köck et al.

    J. Natl. Cancer Inst.

    (1989)
  • J.L. Bennicelli et al.

    Cancer Res.

    (1989)
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