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Fibronectin-induced COX-2 mediates MMP-2 expression and invasiveness of rhabdomyosarcoma

Biochemical and Biophysical Research Communications, ISSN: 0006-291X, Vol: 318, Issue: 2, Page: 594-600
2004
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Article Description

Although accumulating evidence suggests the importance of cyclooxygenase-2 (COX-2) and prostaglandin E 2 (PGE 2 ) in the pathogenesis of many cancers, the mechanism by which this enzyme and its metabolite promote cancer progression is unknown. In this study, we investigated the role of COX-2 in fibronectin-induced up-regulation of rhabdomyosarcoma matrix metalloproteinase (MMP)-2 activity and cellular invasiveness. We tested three human rhabdomyosarcoma cell lines: RMS559, RD, and SJRH30. Cell attachment to fibronectin up-regulated both COX-2 expression and PGE 2 production and concomitantly enhanced MMP-2 activity. Exogenous PGE 2 stimulated MMP-2 promoter activity, increased MMP-2 expression, and increased cellular invasiveness. Aspirin and rofecoxib (non-selective and selective COX-2 inhibitor, respectively) each abolished fibronectin-associated induction of MMP-2 and induced dose-dependent reductions in cellular invasiveness. These data implicated a role for inducible COX-2 and PGE 2 in the regulation of rhabdomyosarcoma cellular invasiveness and MMP-2 activity.

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