Prostaglandin E₂ Increases Growth and Motility of Colorectal Carcinoma Cells

Chronic use of nonsteroidal anti-inflammatory drugs results in a significant 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 inhibit cyclooxygenase activity. The cyclooxygenase enzymes catalyze a key reaction in the conversion of arachidonic acid to prostaglandins, such as prostaglandin E₂ (PGE₂). Here we demonstrate that PGE ₂ treatment of LS-174 human colorectal carcinoma cells leads to increased motility and changes in cell shape. The prostaglandin EP₄ receptor signaling pathway appears to play a role in transducing signals which regulate these effects. PGE₂ treatment results in an activation of phosphatidylinositol 3-kinase/protein kinase B pathway that is required for the PGE₂-induced changes in carcinoma cell motility and colony morphology. Our results suggest that PGE₂ might enhance the invasive potential of colorectal carcinoma cells via activation of major intracellular signal transduction pathways not previously reported to be regulated by prostaglandins.