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


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.
Sundelin
Kaarina
K
Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital, Linköping, Sweden. kaasu@inr.liu.se
Roberg
Karin
K
Grénman
Reidar
R
Håkansson
Leif
L
D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D002460:Cell Line; D045744:Cell Line, Tumor; D016207:Cytokines / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D009062:Mouth Neoplasms / Q000201:enzymology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D017228:Hepatocyte Growth Factor; D020782:Matrix Metalloproteinases