Effects of cytokines on matrix metalloproteinase expression in squamous cell carcinoma in vitro
2007 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, Vol. 125, no 7, 765-773 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2007. Vol. 125, no 7, 765-773 p.
Cytokine, matrix metalloproteinase, oral cancer, squamous cell carcinoma
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-12807DOI: 10.1080/00016480510027484OAI: oai:DiVA.org:liu-12807DiVA: diva2:17092