Fibronectin induces matrix metalloproteinase-2 expression in ovarian cancer cells

OBJECTIVE: To investigate the effects of extracelluar matrix proteins on matrix metalloproteinases (MMPs) expression by cancer cells, and the underlying mechanisms. METHODS: Following stimulation of SKOV3 ovarian cancer cells by fibronectin, MMPs secretion and cellular mRNA contents were assayed by gelatin-zymography and RT-PCR, respectively. The activity of MMP-2 promoter was monitored by cellular luciferase activity after the cells were transfected with MMP-2 promoter-luciferase construct. Cellular p53 contents were determined by Western blot analysis. RESULTS: Fibronectin (5 micrograms/ml) was found to stimulate the secretion of MMP-2 but not MMP-9 by SKOV3 cells. The stimulation was enhanced with the increase in fibronectin concentration. When SKOV3 cells were treated with 10 micrograms/ml fibronectin for 1 hr, the cellular MMP-2 mRNA dramatically increased. However, with increase in stimulation time, MMP-2 mRNA content decreased. Fibronectin induced an increase in luciferase activity in cells transfected with MMP-2 promoter construct, whilst curcumin (50 mumol/L), a potent transcription factor AP-1 inhibitor, could not block the fibronectin-induced increase in MMP-2 promoter activity. Fibronectin also induced an increase in p53 content of SKOV3 cells. CONCLUSION: Fibronectin stimulates ovarian cancer cells to secret MMP-2 via its enhancing effect on MMP-2 promoter activity with resultant increase in MMP-2 transcription. The effect might involve a pathway associated with p53 but independent of AP-1.