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

Hiromichi Ito, Mark Duxbury, Eric Benoit, Robert S. Farivar, James Gardner-Thorpe, Michael J. Zinner, Stanley W. Ashley, Edward E. Whang

Research output: Contribution to journalArticlepeer-review

Abstract

Although accumulating evidence suggests the importance of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) 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 PGE2 production and concomitantly enhanced MMP-2 activity. Exogenous PGE2 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 PGE2 in the regulation of rhabdomyosarcoma cellular invasiveness and MMP-2 activity.

Original languageEnglish (US)
Pages (from-to)594-600
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume318
Issue number2
DOIs
StatePublished - May 28 2004

Keywords

  • COX-2
  • Fibronectin
  • Invasion
  • MMP-2
  • Prostaglandin E
  • Rhabdomyosarcoma

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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