Oxytocin in the tumor microenvironment is associated with lower inflammation and longer survival in advanced epithelial ovarian cancer patients

Michaela G Cuneo; Angela Szeto; Andrew Schrepf; Ellen M Kinner; Benjamin I Schachner; Raisa Ahmed; Premal H Thaker; Michael Goodheart; David Bender; Steve W Cole; Philip M McCabe; Anil K Sood; Susan K Lutgendorf; Armando J Mendez

doi:10.1016/j.psyneuen.2019.04.007

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Oxytocin in the tumor microenvironment is associated with lower inflammation and longer survival in advanced epithelial ovarian cancer patients

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Oxytocin in the tumor microenvironment is associated with lower inflammation and longer survival in advanced epithelial ovarian cancer patients

Michaela G Cuneo, Angela Szeto, Andrew Schrepf, Ellen M Kinner, Benjamin I Schachner, Raisa Ahmed, Premal H Thaker, Michael Goodheart, David Bender, Steve W Cole, …

Psychoneuroendocrinology, Vol.106, pp.244-251

08/2019

DOI: 10.1016/j.psyneuen.2019.04.007

PMID: 31005045

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https://www.ncbi.nlm.nih.gov/pmc/articles/6716948View

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Abstract

Oxytocin is present in the ascites fluid of advanced stage ovarian cancer patients.•Higher ascites oxytocin is associated with lower tumor interleukin-6 and longer survival.•In vitro, oxytocin reduced interleukin-6 secretion from ovarian tumor cells.•Oxytocin may have protective effects in ovarian cancer via anti-inflammatory mechanisms. Prior research demonstrates a protective role for oxytocin in ovarian cancer based on its anti-proliferative, anti-migratory, and anti-invasive effects in vitro and in vivo. However, the role of endogenous oxytocin has not been examined in ovarian cancer patients. Oxytocin also has anti-inflammatory properties that have not been examined in cancer. The purpose of this investigation was to examine relationships between endogenous oxytocin, tumor-associated inflammation (interleukin-6), and survival in advanced epithelial ovarian cancer patients. Tumor microenvironment (ascites) and plasma oxytocin levels were analyzed via ELISA on extracted samples obtained from 79 patients. In vitro models were used to characterize oxytocin and oxytocin receptor expression in four ovarian cancer cell lines and to investigate direct anti-inflammatory effects of oxytocin on tumor cell secretion of interleukin-6. High and variable levels of oxytocin were observed in ascites, up to 200 times greater than in plasma. Higher levels of ascites oxytocin were associated with lower levels of systemic and tumor-associated interleukin-6, an inflammatory cytokine implicated in ovarian tumor progression. Oxytocin also attenuated interleukin-6 secretion from multiple ovarian tumor cell lines in vitro. Higher levels of ascites oxytocin were associated with a significant survival advantage and statistical mediation analyses suggested this effect was partially mediated by interleukin-6. These data identify a previously unacknowledged hormone in the ovarian tumor microenvironment and provide initial evidence that oxytocin has protective effects in ovarian cancer via anti-inflammatory mechanisms. Future studies should examine the therapeutic utility of oxytocin.

Oxytocin

Tumor microenvironment

Ascites

Ovarian neoplasms

interleukin-6

Details

Title: Subtitle: Oxytocin in the tumor microenvironment is associated with lower inflammation and longer survival in advanced epithelial ovarian cancer patients
Creators: Michaela G Cuneo - Department of Psychological & Brain Sciences, University of Iowa, United States
Angela Szeto - Department of Psychology, University of Miami, United States
Andrew Schrepf - Department of Anesthesiology and Chronic Pain and Fatigue Research Center, University of Michigan, United States
Ellen M Kinner - Department of Psychological & Brain Sciences, University of Iowa, United States
Benjamin I Schachner - Diabetes Research Institute, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Miller School of Medicine, University of Miami, United States
Raisa Ahmed - Diabetes Research Institute, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Miller School of Medicine, University of Miami, United States
Premal H Thaker - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, United States
Michael Goodheart - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Iowa, United States
David Bender - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Iowa, United States
Steve W Cole - Department of Medicine, Division of Hematology/Oncology and Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, United States
Philip M McCabe - Department of Psychology, University of Miami, United States
Anil K Sood - Departments of Gynecologic Oncology, Cancer Biology and Center for RNA Interference and Noncoding RNA, University of Texas M.D. Anderson Cancer Center, United States
Susan K Lutgendorf - Department of Psychological & Brain Sciences, University of Iowa, United States
Armando J Mendez - Diabetes Research Institute, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Miller School of Medicine, University of Miami, United States
Resource Type: Journal article
Publication Details: Psychoneuroendocrinology, Vol.106, pp.244-251
DOI: 10.1016/j.psyneuen.2019.04.007
PMID: 31005045
NLM abbreviation: Psychoneuroendocrinology
ISSN: 0306-4530
eISSN: 1873-3360
Publisher: Elsevier Ltd
Grant note: name: NIH, award: CA193249, CA140933, T32GM108540, CA109298, R35 CA209904, AG017265, AG043404, 116387, P30CA086862; DOI: 10.13039/100000048, name: American Cancer Society
Language: English
Date published: 08/2019
Academic Unit: Psychological and Brain Sciences; Iowa Neuroscience Institute; Obstetrics and Gynecology; Urology; Internal Medicine
Record Identifier: 9983930877802771

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