Prostaglandin E-2 increases growth and motility of colorectal carcinoma cells

Chronic use of nonsteroidal anti-inflammatory drugs results in a significan t reduction of risk and mortality from colorectal cancer in humans. All of the mechanism(s) by which nonsteroidal anti-inflammatory drugs exert their protective effects are not completely understood, but they are known to inh ibit cyclooxygenase activity. The cyclooxygenase enzymes catalyze a key rea ction in the conversion of arachidonic acid to prostaglandins, such as pros taglandin E-2 (PGE(2)). Here we demonstrate that PGE(2) treatment of LS-174 human colorectal carcinoma cells leads to increased motility and changes i n cell shape. The prostaglandin EP4 receptor signaling pathway appears to p lay a role in transducing signals which regulate these effects. PGE(2) trea tment results in an activation of phosphatidylinositol 3-kinase/ protein ki nase B pathway that is required for the PGE(2)-induced changes in carcinoma cell motility and colony morphology. Our results suggest that PGE(2) might enhance the invasive potential of colorectal carcinoma cells via activatio n of major intracellular signal transduction pathways not previously report ed to be regulated by prostaglandins.