Overexpression of macrophage migration inhibitory factor induces angiogenesis in human breast cancer

Cancer Lett. 2008 Mar 18;261(2):147-57. doi: 10.1016/j.canlet.2007.11.028. Epub 2008 Jan 2.


Macrophage migration inhibitory factor (MIF) is known to be an important contributor to tumor progression. Overexpression of MIF has been reported in different types of tumors. However, the correlation between MIF expression and tumor pathologic features in patients with breast cancer has not been elucidated. In this study, we examined the expression of MIF, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in human tissues with or without tumor. In addition, we investigated the expression of MIF in MDA-MB-231, MCF-7 (breast cancer cell lines) and MCF-10A (epithelial cell line) cells, and its effect on VEGF and IL-8. We found that MIF was overexpressed in breast cancer tissues compared with normal ones. The level of MIF showed the positive correlation between the expression of IL-8 and tumor microvessel density (MVD). The patients with positive MIF expression in tumor tissues showed a significantly worse disease-free survival compared with negative ones. Increased MIF serum levels were also found to correlate with higher levels of IL-8 in the sera of the patients with breast cancer. In vitro experiments successfully detected MIF in breast cell lines. However, the expression level of it by normal epithelial cells was much less than that of cancer cells. Exogenous MIF did not cause endothelial tube formation and migration but induced a dose dependent increase in VEGF and IL-8 secretion in breast cancer cell lines. In summary, our studies show that human breast cancer tissue expresses MIF. Its in vitro effect on VEGF and IL-8 indicates that MIF may contribute to tumor in angiogenesis and thus play an important role in the pathogenesis of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / metabolism*
  • Blotting, Western
  • Breast Neoplasms / blood supply*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Cell Movement / physiology
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoenzyme Techniques
  • Interleukin-8 / metabolism
  • Intramolecular Oxidoreductases / metabolism*
  • Macrophage Migration-Inhibitory Factors / metabolism*
  • Mastectomy
  • Microcirculation
  • Middle Aged
  • Neovascularization, Pathologic / etiology*
  • Neovascularization, Pathologic / pathology
  • Survival Rate
  • Tissue Array Analysis
  • Tumor Cells, Cultured
  • Umbilical Veins / cytology
  • Umbilical Veins / metabolism
  • Vascular Endothelial Growth Factor A / metabolism


  • Angiogenesis Inducing Agents
  • Interleukin-8
  • Macrophage Migration-Inhibitory Factors
  • Vascular Endothelial Growth Factor A
  • Intramolecular Oxidoreductases
  • MIF protein, human