Oxytocin in the tumor microenvironment is associated with lower inflammation and longer survival in advanced epithelial ovarian cancer patients.
Adult
Aged
Aged, 80 and over
Ascites
/ metabolism
Ascitic Fluid
/ metabolism
Carcinoma, Ovarian Epithelial
/ metabolism
Cell Line, Tumor
Female
Humans
Inflammation
/ metabolism
Interleukin-6
/ analysis
Middle Aged
Ovarian Neoplasms
/ metabolism
Oxytocin
/ metabolism
Receptors, Oxytocin
/ metabolism
Tumor Microenvironment
Ascites
Ovarian neoplasms
Oxytocin
Tumor microenvironment
interleukin-6
Journal
Psychoneuroendocrinology
ISSN: 1873-3360
Titre abrégé: Psychoneuroendocrinology
Pays: England
ID NLM: 7612148
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
23
01
2019
revised:
21
03
2019
accepted:
05
04
2019
pubmed:
21
4
2019
medline:
1
4
2020
entrez:
21
4
2019
Statut:
ppublish
Résumé
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.
Sections du résumé
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.
Identifiants
pubmed: 31005045
pii: S0306-4530(19)30064-2
doi: 10.1016/j.psyneuen.2019.04.007
pmc: PMC6716948
mid: NIHMS1527306
pii:
doi:
Substances chimiques
Interleukin-6
0
Receptors, Oxytocin
0
Oxytocin
50-56-6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
244-251Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL116387
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA140933
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA086862
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM108540
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA109298
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA209904
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA193249
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG017265
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG043404
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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