STIMULATION OF PROSTAGLANDIN PRODUCTION BY HEPATOCYTE GROWTH-FACTOR IN HUMAN GASTRIC-CARCINOMA CELLS

Hepatocyte growth factor (HGF), a protein with pleiotropic biological activity affecting cell growth and motility, was found to markedly act ivate prostaglandin production in human gastric carcinoma TMK-1 cells. HPLC analysis revealed that HGF stimulated the production of prostagl andin E2 (PGE2), which is the major prostaglandin produced in these ce lls. HGF maximally stimulated PGE2 production at a concentration of 10 ng/ml, and it was a more potent stimulator of PGE2 production than ep idermal growth factor (EGF), which is known to stimulate prostaglandin production in various cell lines. The simultaneous addition of HGF an d EGF caused no further stimulation of the PGE2 production observed in HGF-treated cells. We showed also that HGF increased the arachidonate release from TMK-1 cells, which release was completely suppressed by the addition of phospholipase A2 (PLA2) inhibitors. Further studies in vitro showed that HGF enhanced cellular activities of cytosolic PLA2 and cyclooxygenase 1.5-fold each. These results indicate that HGF stim ulates prostaglandin production through increases in both cytosolic PL A2 and cyclooxygenase activities.