Effects of tumor necrosis factor-α and interferon-γ on expressions of matrix metalloproteinase-2 and -9 in human bladder cancer cells

We have investigated the effects of tumor necrosis factor-α (TNF-α) and interferon (INF-γ), the potent Bacillus Calmette–Guerin (BCG)-induced cytokines on the production of MMP-2, MMP-9, TIMP-1, TIMP-2 and MT1-MMP in high grade human bladder cancer cell lines, T-24, J-82 and HT-1376 cell lines. MMP-2 expression and activity were decreased in T-24 cells treated with both cytokines in a dose dependent manner. However, J-82 cells treated with TNF-α and INF-γ revealed dose dependent increases of MMP-9 expression and activity with similar baseline expression and activity of MMP-2. HT-1376 cells after exposure to TNF-α only enhanced the expression and activity of MMP-9. These results indicate that TNF-α and INF-γ could regulate the production of MMP-2 or MMP-9 on bladder cancer cells and their patterns of regulation are cell specific. Furthermore, this diverse response of bladder cancer cells to TNF-α and INF-γ suggests that BCG immunotherapy may enhance the invasiveness of bladder cancer in certain conditions with induction of MMPs.