Effects of cytokines on matrix metalloproteinase expression in squamous cell carcinoma in vitro

• Objective: MMPs play an important role in enhanced intra-tumoral proteolytic activity, promoting angiogenesis and invasion by acting on extracellular matrix substances. Cytokines secreted by tumour-infiltrating immune cells, fibroblasts and tumour cells can modulate MMP expression and secretion by cancer cells. The objective of this study was to investigate the effects of IL-6, soluble IL-6 receptor (sIL-6R), HGF, TNF- and IL-8 on MMP-1, -2 and -9 expression by two oral squamous cell carcinoma cell lines (UT-SCC-20A and -24A). Material and methods: ELISA was used to analyse secretion of total MMP protein and gelatin zymography was used for activity analysis. Results: IL-6 had a moderate stimulatory effect on MMP-1 secretion in both cell lines, whereas sIL-6R had no effect. When these cytokines were added together, a dose-dependent, synergistic stimulatory effect was observed. HGF also upregulated MMP-1 secretion, especially in one cell line (UT-SCC-24A), and a synergistic effect was observed when HGF was added to IL-6 in both cell lines. MMP-9 secretion by UT-SCC-24A was increased when stimulated with HGF and IL-6 combined with sIL-6R, whereas no effect was found in the other cell line. TNF- stimulated MMP-9 secretion in both cell lines, but only stimulated MMP-1 secretion in one (UT-SCC-24A). The zymographic results were consistent with the ELISA results, indicating an upregulation of active enzyme when a stimulatory effect on protein expression was detected. Conclusions: The intra-tumoral cytokines IL-6, hepatocyte growth factor (HGF) and tumour necrosis factor- (TNF-) stimulate oral cancer cells to enhanced secretion of matrix metalloproteinase (MMP)-1 and -9. These results contribute to an understanding of the extracellular events necessary for tumour progression.

Nyckelord

Cytokine

matrix metalloproteinase

oral cancer

squamous cell carcinoma

MEDICINE

MEDICIN

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