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Carcinogenesis Advance Access originally published online on September 9, 2004
Carcinogenesis 2005 26(1):11-15; doi:10.1093/carcin/bgh279
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Carcinogenesis vol.26 no.1 © Oxford University Press 2005; all rights reserved.

ARTICLE

Expression of macrophage migration inhibitory factor in esophageal squamous cell carcinoma and effects of bile acids and NSAIDs

Harry Hua-Xiang Xia1, Shu Tian Zhang2, Shiu Kum Lam1, Marie Chia-Mi Lin3, Hsiang Fu Kung3 and Benjamin Chun-Yu Wong1,4

1 Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, 2 Department of Medicine, Beijing Friendship Hospital, Capital University of Medical Sciences, Beijing, China and 3 Institute of Molecular Biology, The University of Hong Kong, Hong Kong

4 To whom correspondence should be addressed Email: bcywong{at}hku.hk

The aim of this study was to determine the macrophage migration inhibitory factor (MIF) protein and mRNA expression in esophageal squamous cell carcinoma (ESCC), and the effect of bile acids, aspirin and a selective cyclooxygenase-2 (COX-2) inhibitor, NS398, on MIF expression in ESCC cells in vitro. Specimens from tumors and the adjacent non-cancerous tissues were obtained from 52 ESCC patients. Western blotting was used for the detection of MIF protein expression, and reverse transcription–polymerase chain reaction (RT–PCR) for MIF mRNA expression. Cells of an ESCC cell line, Eca-109, were treated with chenodeoxycholate (CD, 100 mM), glycochenodeoxycholate (GCD, 1 mM), aspirin (1 mM) or NS398 (1 µM). Enzyme-linked immunosorbent assay (ELISA) and RT–PCR were used to detect the expression of the MIF protein and mRNA, respectively, in the supernatant and cultured cells. Western blotting demonstrated that levels of MIF protein were increased in tumors versus non-malignant tissues, with the expression ratio of MIF over ß-actin of 0.93 ± 0.21 and 0.57 ± 0.08, respectively (P = 0.012). In vitro, both CD and GCD induced a dramatic increase in MIF protein and mRNA in ESCC cells. On the other hand, aspirin and NS398 significantly decreased MIF protein and mRNA expression, and completely blocked bile acid-induced MIF synthesis in the presence or absence of prostaglandin E2. In conclusion, MIF expression is increased in ESCC. Whereas bile acids induce MIF expression in ESCC cells, aspirin and NS398 significantly inhibit MIF expression, even in the presence of bile acids, via a COX-independent mechanism.


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