The inhibitory effect of norepinephrine on the migration of ES-2 ovarian carcinoma cells involves a Rap1-dependent pathway.

Our previous studies have shown that norepinephrine induces the migratory activity of human PC-3 prostate, SW 480 colon and MDA-MB-468 breast carcinoma cells. In contrast to these results, we show here that human ES-2 ovarian carcinoma cells have a reduced migratory activity after norepinephrine treatment. This inhibitory effect is possibly mediated by a cAMP-dependent activation of the small GTPase Rap1 via Epac. Furthermore, a key signalling event of the promigratory effect of norepinephrine in the above mentioned carcinoma cells is the activation of phospholipase C enzymes. In ES-2 cells, this part of the signalling cascade is constitutively active.