PGE(2) is generated by specific COX-2 activity and increases VEGF production in COX-2-expressing human pancreatic cancer cells

Biochem Biophys Res Commun. 2003 Jul 11;306(4):887-97. doi: 10.1016/s0006-291x(03)01079-9.

Abstract

In some cancers cyclooxygenase (COX) inhibition appears to be anti-mitogenic and anti-angiogenic, but the actions of COX-derived prostaglandins in pancreatic cancer (PaCa) are unknown. In this study COX-2 was detected in three of six PaCa cell lines while COX-1 was identified in all cell lines. COX-2 expression correlated with basal and arachidonic acid (AA) stimulated PGE(2) production. PGE(2) production was inhibited by the COX-2 inhibitor nimesulide. In COX-2 expressing cells, exogenous AA and PGE(2) increased VEGF synthesis via the EP(2) receptor. Whereas PGE(2) stimulated intracellular cAMP formation in COX-2 positive and negative cells, 8-bromo cAMP stimulated VEGF production only in COX-2 expressing cells. Stimulating COX-2 expressing PaCa cell lines with AA enhanced migration of endothelial cells, an effect which was inhibited by a COX-2 inhibitor and EP(2) receptor antagonist. These data identify a subset of human PaCa cell lines that express functional COX-2 enzyme. PGE(2) generated by specific COX-2 activity increases VEGF secretion in human PaCa cells through an autocrine mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / metabolism
  • Arachidonic Acid / metabolism
  • Arachidonic Acid / pharmacology
  • Blotting, Western
  • Cell Movement
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Dinoprostone / biosynthesis*
  • Dose-Response Relationship, Drug
  • Endothelial Growth Factors / biosynthesis*
  • Endothelium, Vascular / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Isoenzymes / metabolism*
  • Lymphokines / biosynthesis*
  • Membrane Proteins
  • Models, Biological
  • Pancreatic Neoplasms / enzymology*
  • Pancreatic Neoplasms / metabolism*
  • Plasmids / metabolism
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfonamides / pharmacology
  • Time Factors
  • Transfection
  • Tumor Cells, Cultured
  • 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
  • Sulfonamides
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Arachidonic Acid
  • Cyclic AMP
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • nimesulide