Macrophage migration inhibitory factor (MIF): Its potential role in tumor growth and tumor-associated angiogenesis.

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 fully 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 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 the 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 control mice.