Biological relevance of oxytocin and oxytocin receptors in cancer cells and primary tumors

For a long time, the hypothalamic nonapeptide oxytocin (OT) is known to pla y a crucial role in many reproductive and behavioral functions. In recent y ears, a new biological effect of OT has been identified in neoplastic patho logy. In this context, OT acts as a growth regulator, through the activatio n of specific G-coupled transmembrane receptors (OTR). In vitro, an antipro liferative effect of OT was demonstrated in neoplastic cells of either epit helial (mammary and endometrial) or nervous or bone origin, all expressing OTR. Furthermore, the growth-inhibiting effect of OT was also tested and co nfirmed in mouse and rat mammary carcinomas in vivo. In neoplastic cells fr om another OT target tissue, trophoblast, the OT effect was to promote prol iferation, the opposite of what previously observed in all the other neopla stic OT responsive cells. The signal transduction involved in the OT biolog ical effect was different in OT growth-inhibited or growth-stimulated cells . In the former, the OT effect was mediated by the activation of the cAMP-P KA pathway, a non-conventional OT signaling, whereas in the latter by the i ncrease of intracellular calcium and tyrosine phosphorylation, which are th e 'classical' OT transducers. The unexpected role of OT (and OT analogues) in regulating cell proliferation, as well as the diffuse expression of OTR in neoplastic tissue of different origin, open new perspectives on the biol ogical role of the OT-OTR system in cancer.