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

Abstract:

CONCLUSIONS:The intra-tumoral cytokines IL-6, hepatocyte growth factor (HGF) and tumour necrosis factor-a (TNF-a) 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. 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-a 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-a 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.

journal_name

Acta Otolaryngol

journal_title

Acta oto-laryngologica

authors

Sundelin K,Roberg K,Grénman R,Håkansson L

doi

10.1080/00016480510027484

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

765-73

issue

7

eissn

0001-6489

issn

1651-2251

pii

HA0B2M980VVE485R

journal_volume

125

pub_type

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