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
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Research Support, Non-U.S. Gov't
MeSH terms
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8-Bromo Cyclic Adenosine Monophosphate / metabolism
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Arachidonic Acid / metabolism
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Arachidonic Acid / pharmacology
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Blotting, Western
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Cell Movement
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Cells, Cultured
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Cyclic AMP / metabolism
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / pharmacology
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Dinoprostone / biosynthesis*
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Dose-Response Relationship, Drug
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Endothelial Growth Factors / biosynthesis*
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Endothelium, Vascular / metabolism
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Humans
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Intercellular Signaling Peptides and Proteins / biosynthesis*
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Isoenzymes / metabolism*
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Lymphokines / biosynthesis*
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Membrane Proteins
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Models, Biological
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Pancreatic Neoplasms / enzymology*
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Pancreatic Neoplasms / metabolism*
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Plasmids / metabolism
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Prostaglandin-Endoperoxide Synthases / metabolism*
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sulfonamides / pharmacology
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Time Factors
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Transfection
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Tumor Cells, Cultured
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Endothelial Growth Factors
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Intercellular Signaling Peptides and Proteins
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Isoenzymes
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Lymphokines
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Membrane Proteins
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RNA, Messenger
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Sulfonamides
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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8-Bromo Cyclic Adenosine Monophosphate
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Arachidonic Acid
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Cyclic AMP
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Dinoprostone
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nimesulide