Investigating the Role of Cortisol and Oxytocin Signalling in Human Ovarian Cancer

Abstract

With over 4000 deaths a year and a 10-year survival rate of just 35% it’s understandable why patients with ovarian cancer report high levels of distress. Emerging data associate psychological behaviour with prevalence and stress with negative impact on prognosis. Knowing the molecular interactions in ovarian cancer cells involved with better social support could help prevent shorter survival outcomes. Elevated levels of the stress hormone cortisol (C) have been associated with tumour cell proliferation whilst emerging studies link the social hormone oxytocin (OT) with having a moderating role on stress. We hypothesise that there is a cross-talk between these two hormones at a molecular level. Three ovarian cancer cell lines were used as in-vitro models; SKOV3, PEO1 and MDAH-2774, and treated with C at concentrations representative of physiological stress in vivo in the presence or absence of OT. In all three cell lines OT reduced cell proliferation and migration, induced apoptosis and autophagy and partially reversed the effects of C providing evidence of cross-talk in vitro. OT was shown to drive alternative splicing of the glucocorticoid receptor (GR) in a cell specific manner. Quantitative RT-PCR from ovarian cancer tissues revealed that the glucocorticoid receptor (splice variant GR-P) and oxytocin receptor (OTR) were significantly upregulated compared to normal ovarian tissues. Tissue microarray revealed that the expression of GRα was lower in early stage ovarian cancer tissue compared to late stage. Data provided in this study explains why social support could be used to help distressed ovarian cancer patients and could potentially be used to produce new therapeutic interventions for socially isolated patients.