Effect of prostaglandin E-1 on vascular endothelial growth factor production by human macrophages and colon cancer cells

We previously demonstrated that cyclooxygenase-2 (COX-2) was predominantly expressed in macrophages of sporadic human colonic adenomas; however, the r ole of COX-2-expressing cells during colon carcinogenesis has not yet been elucidated. In the present study, we showed the effect of PGE, on vascular endothelial growth factor (VEGF) production by PMA-differentiated U937 cell s, a human macrophage model (H-Mac), and by human colon cancer cells T84. P GE(1) dramatically induced VEGF production by H-Mac, but not that by T84. P GE(1) significantly increased intracellular cAMP formation by H-Mac, but on ly modestly increased that by T84. 8-bromo-cAMP and cholera toxin also incr eased VECF production by H-Mac. In contrast, neither of these agents modula ted VEGF production by T84. EP2 and EP4 (PGE specific receptors) mRNA was e xpressed in both cells. PG dramatically increased VEGF production by activa ted macrophages, but not by cancer cells, through a specific PGE receptor-m ediated process. These findings suggest that PGs produced by COX-2-expressi ng macrophages induce VEGF pro duct ion by macrophages, but not by cancer c ells, in an autocrine fashion.