The Analysis of Macrophage Migration Inhibitory Factor (MIF) Functions using MIF Transgenic Mice

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Macrophage migration inhibitory factor (MIF) functions as a pluripotent cytokine involved in broad-spectrum pathophysiological events in association with inflammation and immune responses. Several reports, including ours, have suggested that MIF is also involved in tumorigenesis ; however, its precise role has not been folly investigated. We examined the effectiveness of anti-MIF antibodies on tumor growth and tumor-associated angiogenesis using murine colon cancer cell line colon 26. We observed a significant inhibition of growth of tumors embedded on the back of BALB/c mice by the treatment with anti-MIF antibodies. Next, we implanted a Millipore chamber filled with colon cancer cells in the subcutaneous fascia of the flanks of mice, and then treated them with anti-MIF antibodies. We found that angiogenesis was markedly suppressed within the region of subcutaneous fascia that was in contact with the chamber. To further assess the role of MIF in tumorigenesis, we established MIF transgenic mice, which demonstrated that tumor growth and the associated angiogenesis were significantly enhanced in comparison with the control mice.