[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.


CONCLUSIONS
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.
Yan
C
C
Department of Tumor Molecular Biology, Research Clinic, Academy of Military Medical Sciences, Beijing 100850, China.
Li
C
C
Tian
F
F
D005260:Female; D005353:Fibronectins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D005353:Fibronectins; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; D020778:Matrix Metalloproteinase 2