Cyclooxygenase-2 increased the angiogenic and metastatic potential of tumor cells

Biochem Biophys Res Commun. 2002 Dec 20;299(5):886-90. doi: 10.1016/s0006-291x(02)02707-9.

Abstract

It seems certain that COX-2 is related to tumor and some data suggested that COX-2 might have relation to tumor malignance and angiogenesis. In order to elucidate the relationship between COX-2 and tumor invasive and angiogenic ability, we transfected human transitional cell carcinoma (TCC) cell line, EJ, permanently with a COX-2 expression vector or the mock vector. The EJ-COX(2) cells, which overexpressed COX-2, acquired increased invasiveness and angiogenic ability by activation of VEGF, uPA, and MMP-2. Increased invasiveness and angiogenic ability were reversed by treatment with either selective COX-2 inhibitor, NS-398, or dual COX inhibitor, indomethacin. These results demonstrate that overexpression of COX-2 can lead to phenotypic changes that alter the metastatic and angiogenic potential of TCC cancer cells.

MeSH terms

  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / metabolism*
  • Carcinoma, Transitional Cell / pathology
  • Cell Line
  • Cell Movement* / drug effects
  • Coculture Techniques
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Endothelial Growth Factors / biosynthesis
  • Endothelial Growth Factors / genetics
  • Endothelium, Vascular / physiology
  • Humans
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • Intercellular Signaling Peptides and Proteins / genetics
  • Isoenzymes / genetics
  • Isoenzymes / physiology*
  • Lymphokines / biosynthesis
  • Lymphokines / genetics
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 2 / genetics
  • Membrane Proteins
  • Neoplasm Metastasis
  • Neovascularization, Pathologic
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / physiology*
  • RNA, Messenger / biosynthesis
  • Transfection
  • Tumor Cells, Cultured
  • Urokinase-Type Plasminogen Activator / biosynthesis
  • Urokinase-Type Plasminogen Activator / genetics
  • Urologic Neoplasms / genetics
  • Urologic Neoplasms / metabolism*
  • Urologic Neoplasms / pathology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Isoenzymes
  • Lymphokines
  • Membrane Proteins
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinase 2