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Macrophage migration inhibitory factor (MIF): Its potential role in tumor growth and tumor-associated angiogenesis
Jun Nishihira1, Teruo Ishibashi, Tsuyoshi Fukushima
1Department of Molecular Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. j_nisihi@med.hokudai.ac.jp
Abstract:
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.
Insights
Anti-macrophage migration inhibitory factor (MIF) antibodies effectively inhibited colon cancer growth and angiogenesis in mice. MIF overexpression in transgenic mice significantly enhanced tumor growth and associated angiogenesis.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine implicated in inflammation and immune responses.
- Emerging evidence suggests MIF plays a role in tumorigenesis, but its precise function requires further investigation.
Purpose of the Study:
- To investigate the role of MIF in tumor growth and angiogenesis.
- To evaluate the therapeutic potential of anti-MIF antibodies in a murine colon cancer model.
Main Methods:
- Treatment of tumor-bearing BALB/c mice with anti-MIF antibodies.
- Assessment of tumor growth and tumor-associated angiogenesis using a Millipore chamber model.
- Generation and analysis of MIF transgenic mice to study enhanced tumorigenesis.
Main Results:
- Anti-MIF antibody treatment significantly inhibited colon cancer tumor growth in mice.
- Angiogenesis within the tumor microenvironment was markedly suppressed by anti-MIF antibodies.
- MIF transgenic mice exhibited significantly enhanced tumor growth and angiogenesis compared to controls.
Conclusions:
- MIF plays a critical role in promoting tumor growth and angiogenesis.
- Targeting MIF with antibodies represents a potential therapeutic strategy for colon cancer.
- Modulation of MIF activity offers a promising avenue for cancer treatment.