Abstract # 2041 Biobehavioral effects on epithelial mesenchymal transition in ovarian cancer

Abstract

Epithelial mesenchymal transition (EMT) is a process by which transformed epithelial cells undergo changes to a more mesenchymal phenotype, thereby enhancing metastasis. We examined effects of beta-adrenergic signaling and/or biobehavioral exposures on EMT polarization in primary ovarian tumor cells and in exosomes, cell-derived vesicles involved in intercellular signaling. Exosomal profiles from 40 ovarian cancer patients with low vs. high social support were examined for EMT polarization. We recently reported a significant up-regulation of 67 mesenchymal-characteristic gene transcripts and down-regulation of 63 epithelial-characteristic transcripts in exosomes of patients with low levels of social support, demonstrating increased EMT polarization (p = 0.0002). Here, genome-wide transcriptome profiling of advanced stage ovarian tumors from 98 patients was performed, and EMT profiles of those above vs. below a median split on tumor norepinephrine (NE) were compared, adjusting for clinical covariates. In vitro stimulation of ovarian cancer cells with NE assessed effects of NE exposure on EMT mediators. High NE tumors showed significant polarization to a more mesenchymal phenotype, as well as decreased expression of a variety of anti-metastatic genes. In two ovarian cancer cell lines, exposure to stress-concentrations of NE significantly increased transcription of EMT mediators SNAI1, SNAI2, and IL6. Induction of EMT gene expression programs by biobehavioral factors and beta-adrenergic signaling provide a plausible pathway through which biobehavioral risk factors may promote ovarian cancer progression.