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Open Access Highly Accessed Research article

Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells

Katherine L Meyer-Siegler12*, Erica C Leifheit13 and Pedro L Vera12

Author Affiliations

1 Research & Development Service (151), Bay Pines VA Medical Center, Bay Pines, FL 33744, USA

2 Department of Surgery, Division of Urology, University of South Florida, Tampa, FL 33612, USA

3 Department of Natural Sciences, Eckerd College, St. Petersburg, FL 33711, USA

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BMC Cancer 2004, 4:34  doi:10.1186/1471-2407-4-34

Published: 12 July 2004

Abstract

Background

The importance of various inflammatory cytokines in maintaining tumor cell growth and viability is well established. Increased expression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) has previously been associated with various types of adenocarcinoma.

Methods

MIF IHC was used to localize MIF in human bladder tissue. ELISA and Western blot analysis determined the synthesis and secretion of MIF by human bladder transitional cell carcinoma cells. The effects of MIF inhibitors (high molecular weight hyaluronate (HA), anti-MIF antibody or MIF anti-sense) on cell growth and cytokine expression were analyzed.

Results

Human bladder cancer cells (HT-1376) secrete detectable amounts of MIF protein. Treatment with HA, anti-MIF antibody and MIF anti-sense reduced HT-1376 cell proliferation, MIF protein secretion, MIF gene expression and secreted inflammatory cytokines. Our evidence suggests MIF interacts with the invariant chain, CD74 and the major cell surface receptor for HA, CD44.

Conclusions

This study is the first to report MIF expression in the human bladder and these findings support a role for MIF in tumor cell proliferation. Since MIF participates in the inflammatory response and bladder cancer is associated with chronic inflammatory conditions, these new findings suggest that neutralizing bladder tumor MIF may serve as a novel therapeutic treatment for bladder carcinoma.