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 play a crucial role in many reproductive and behavioral functions. In recent years, a new biological effect of OT has been identified in neoplastic pathology. In this context, OT acts as a growth regulator, through the activation of specific G-coupled transmembrane receptors (OTR). In vitro, an antiproliferative effect of OT was demonstrated in neoplastic cells of either epithelial (mammary and endometrial) or nervous or bone origin, all expressing OTR. Furthermore, the growth-inhibiting effect of OT was also tested and confirmed in mouse and rat mammary carcinomas in vivo. In neoplastic cells from another OT target tissue, trophoblast, the OT effect was to promote proliferation, the opposite of what previously observed in all the other neoplastic OT responsive cells. The signal transduction involved in the OT biological 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-PKA pathway, a non-conventional OT signaling, whereas in the latter by the increase of intracellular calcium and tyrosine phosphorylation, which are the '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 biological role of the OT-OTR system in cancer.