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

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.