Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1586, Issue 1, Pages 11-22Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0925-4439(01)00080-1
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Matrix metalloproteinase-9 (MMP-9) produced by tumor cells is known to be implicated in the invasion of squamous cell carcinoma (SCC). In the process of searching for agents to inhibit MMP-9 in cancer, immunosuppressive factors, dexamethasone (DEX) and interleukin-4 (IL-4) were found to inhibit protein production as well as gene expression of MMP9 in tumor necrosis factor alpha (TNFalpha)-stimulated SCC cells. DEX and IL-4 could also suppress the expression of urokinase type plasminogen activator (uPA) to prevent the conversion from the proenzyme form of MMP-9 to its active form. Regarding their mechanisms to inhibit the expression of MMP-9 and uPA, DEX and IL-4 had no effect on the cell surface levels of TNFalpha receptors, but inhibited the activation of NF-kappaB and NF-kappaB-dependent gene expression. DEX, but not IL-4, could strongly augment the TNFalpha-induced expression of IkappaBalpha in SCC cells. These results suggest that DEX and IL-4 suppress not only immunological reactions, but also tumor invasion by targeting NF-kappaB. (C) 2002 Elsevier Science B.V. All rights reserved.
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