Macrophage migration inhibitory factor increases MMP-2 activity in DU-145 prostate cells

Macrophage migration inhibitory factor (MIF) is a cytokine expressed by a number of different cell types and has been detected in prostatic glandular epithelial cells by immunohistochemistry. The goal of this study was to determine if in vitro cultured prostate cells produce this protein and some of the effects of MIF on these cells. Proliferation of normal prostate cells, the BPH-1 and DU-145 established cell lines in the presence of MIF were assessed. ELISA was used to screen conditioned medium for the production of MIF, matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2). Zymogram electrophoresis gels determined the activities of secreted MMP-2. The amount of MIF in the conditioned medium detected after 72 h of growth in normal, BPH-1 and DU-145 cells was 2.9, 5.2 and 10.2 ng/ml/10(6)cells respectively. Exogenous addition of MIF (25 ng/ml) to cells cultured in vitro stimulated proliferation of all the cell types tested. MIF addition to proliferating DU-145 cells resulted in a two-fold increase in the relative amount of active MMP-2 as determined by zymogram gel analysis of conditioned medium.