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1: Mol Med. 2008 Nov 9. [Epub ahead of print]
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Macrophage Migration Inhibitory Factor (MIF) Promotes Colorectal Cancer.

He XX, Chen K, Yang J, Li XY, Gan HY, Lin CY, Coleman TR, Al-Abed Y.

Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou Medical College, 250 Changgang East Road, Guangzhou, Guangdong 510260, China.

A growing body of evidence implicates macrophage migration inhibitory factor (MIF) in tumorigenesis and metastasis. In this study, we investigated whether MIF expression was associated with clinicopathologic features of colorectal carcinoma (CRC), especially in tumors with hepatic metastasis, and whether neutralization of endogenous MIF using anti-MIF therapeutics would inhibit tumor growth and/or decrease the frequency of colorectal hepatic metastases in a mouse colon carcinoma model. The concentration of serum MIF was positively correlated with an increased risk of hepatic metastasis in human patients with CRC (R = 1.25, 95% confidence internal = 1.02-1.52, p = 0.03). MIF was also dramatically up-regulated in human colorectal tissue with 20-40 times as many MIF positive cells in the mucosa of patients with CRC versus that found in normal tissue (p<0.001 ANOVA). Moreover, in those patients with metastatic colorectal cancer in the liver, MIF positive cells were similarly increased in the diseased hepatic tissue. This increased MIF expression was restricted to diseased tissue and not found in areas of the liver with normal morphology. In subsequent in vitro experiments, we found that addition of recombinant MIF to colonic cell lines significantly increased their invasive properties and expression of several genes (e.g., MMP-9 and VEGF) known to be up-regulated in cancerous tissue. Finally, we treated mice containing CT26 colon carcinoma cell transplants with anti-MIF therapeutics - either the MIF-specific inhibitor ISO-1 or neutralizing anti-MIF antibodies - and observed a significant reduction in tumor burden relative to vehicle-treated animals. Taken together, these data demonstrates that MIF expression is not only correlated with colorectal cancer state but also may play a direct role in cancer development.

PMID: 19009023 [PubMed - as supplied by publisher]

PMCID: PMC2581606