Oxytocin stimulates migration and invasion in human endothelial cells

Background and purpose. It has recently been reported that oxytocin (OT) is produced by some tumoral cell types, and that OT receptors (OTRs) belonging to the G protein-coupled receptor (GPCR) family are expressed in a variety of cell types. Among these, human umbilical vein endothelial cells (HUVECs) respond to OT with an increased proliferation, suggesting a possible role for the hormone in the regulation of angiogenesis. Experimental approach. We employed chemotaxis and chemoinvasion assays to characterize the effect of OT on HUVEC motility, and immunoblot analysis to study its molecular mechanisms of action. Key results. We showed that OT stimulates migration and invasion in HUVECs via OTR activation. Searching for the molecular mechanism(s) responsible for OT’s pro-migratory effect, we identified the Gq coupling of OTRs and phospholipase C (PLC) as the main effectors of OT’s action in HUVECs. We also found that OT stimulates the phosphorylation of endothelial nitric oxide synthase (eNOS) via the phosphatidylinositol-3-kinase (PI-3-K)/AKT pathway, and that the activation of PI-3-K and formation of nitric oxide (NO) are required for the pro-migratory effect of OT. Conclusions and implications. The ability of OT to stimulate HUVEC motility and invasion suggests that the hormone can participate to physiopathological processes where activation of endothelial cells plays an important role, like for example angiogenesis. Interestingly, both the AKT and eNOS phosphorylation induced by OTR activation depend on PLC activity, thus suggesting the existence of a still undefined mechanism connecting PLC to the PI-3-K/AKT pathway upon OT stimulation.