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Cited by 18Ovarian cancer diagnosis and treatmentCancer, Stress, Anesthesia, and Immune ResponseCytokine Signaling Pathways and Interactions

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

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Cuneo, Michaela G., Szeto, Angela, Schrepf, Andrew, Kinner, Ellen M., Schachner, Benjamin I., Ahmed, Raisa, Thaker, Premal H., Goodheart, Michael +6 more·2019·Psychoneuroendocrinology
DOI 10.1016/j.psyneuen.2019.04.007PMC PMC6716948
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Abstract

Background 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. Methods 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. Conclusions 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.

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  • In patients with ovarian cancer, high levels of OT, both in the plasma and locally at tumors, are associated with lower levels of an inflammatory cytokine implicated in ovarian tumors.

    “In patients with ovarian cancer, high levels of OT, both in the plasma and locally at tumors, are associated with lower levels of an inflammatory cytokine implicated in ovarian tumors [180].”

    From The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives (2023) · cites this paper as [180]

    The Results section reports that higher oxytocin in ascites was associated with lower interleukin-6 in both ascites and plasma. It also reports that plasma oxytocin was not related to interleukin-6 in either location, so the claim is unsupported for high plasma oxytocin. Page numbers were not supplied. (LLM, conf=0.93)

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  • Patients with high OT levels at the location of the tumor had a 34% decreased risk of death from the disease compared to patients with low OT levels.

    “Patients with high OT levels at the location of the tumor had a 34% decreased risk of death from the disease compared to patients with low OT levels.”

    From The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives (2023) · cites this paper as [180]

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Authors
Cuneo, M. G., Szeto, A., Schrepf, A., Kinner, E. M., Schachner, B. I., Ahmed, R., Thaker, P. H., Goodheart, M., Bender, D., Cole, S. W., McCabe, P. M., Sood, A. K., Lutgendorf, S. K., & Mendez, A. J.
Affiliations
  • University of Iowa (US)
  • University of Miami (US)
  • University of Michigan (US)
  • Washington University in St. Louis (US)
  • University of California, Los Angeles (US)
  • The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Lutgendorf, Susan K.
ORCID
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2019-08
Volume
106
Pages
244-251
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/j.psyneuen.2019.04.007
PMC
PMC6716948
OpenAlex
W2929809684
Cited by
18
References
38
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 3
FWCI
2.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIH (CA193249, CA140933, T32GM108540, CA109298, R35 CA209904, AG017265, AG043404, 116387, P30CA086862)
  • American Cancer Society
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
  • Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
oxytocin, epithelial ovarian cancer, tumor microenvironment, ascites, tumor inflammation, interleukin-6, survival, oxytocin receptor, anti-inflammatory activity, tumor progression, hormone therapy
MeSH terms
Carcinoma, Ovarian Epithelial, Adult, Aged, Aged, 80 and over, Ascites, Ascitic Fluid, Female, Humans, Inflammation, Middle Aged, Ovarian Neoplasms, Oxytocin, Interleukin-6, Receptors, Oxytocin, Cell Line, Tumor, Tumor Microenvironment

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