Abstract
We have investigated the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon (INF-gamma), 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-alpha and INF-gamma 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-alpha only enhanced the expression and activity of MMP-9. These results indicate that TNF-alpha and INF-gamma 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-alpha and INF-gamma suggests that BCG immunotherapy may enhance the invasiveness of bladder cancer in certain conditions with induction of MMPs.
MeSH terms
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Dose-Response Relationship, Drug
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Gene Expression Regulation, Enzymologic / drug effects
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Interferon-gamma / pharmacology*
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Matrix Metalloproteinase 2 / genetics*
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 9 / genetics*
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Matrix Metalloproteinase 9 / metabolism
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Matrix Metalloproteinases, Membrane-Associated
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Metalloendopeptidases / genetics
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RNA, Messenger / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Tissue Inhibitor of Metalloproteinase-1 / genetics
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Tissue Inhibitor of Metalloproteinase-2 / genetics
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / pharmacology*
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Urinary Bladder Neoplasms / enzymology
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Urinary Bladder Neoplasms / pathology
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Urinary Bladder Neoplasms / prevention & control*
Substances
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RNA, Messenger
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Tissue Inhibitor of Metalloproteinase-1
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Tumor Necrosis Factor-alpha
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Tissue Inhibitor of Metalloproteinase-2
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Interferon-gamma
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Matrix Metalloproteinases, Membrane-Associated
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Metalloendopeptidases
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9