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

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

doi:10.1016/j.psyneuen.2019.04.007

Cited by 14 publications

(22 citation statements)

References 33 publications

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“…Moreover, the quality of life of patients is greatly reduced, and poor prognosis or drug resistance may result ( 37 ). Some studies have shown that epigenetic changes are related to cancer occurrence and progression ( 38 ), so we inferred that considering epigenetic factors in curing cancer patients will help alleviate these problems. BRD9 is one of the epigenetic readers in clinical settings and is universal in a range of cancers, and the rate of changes in gastric cancer is 26%.…”

Section: Discussionmentioning

confidence: 99%

BRD9 controls the oxytocin signaling pathway in gastric cancer via CANA2D4, CALML6, GNAO1, and KCNJ5

Wang¹,

Jiang²,

Yu³

2020

Transl Cancer Res TCR

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Background First-line chemotherapeutic agents lead to remarkable activation treatment in cancers, but the side effects of these drugs also damage healthy cells. In some cases, drug resistance to chemotherapeutic agents is induced in cancer cells. The molecular mechanisms underlying such a side effect have been studied in a range of cancer types, yet little is known about how the adverse effects of chemotherapeutic drugs can be diminished by targeting bromodomain-containing protein 9 (BRD9) in gastric cancers. Methods We used two gastric cancer cell lines (MGC-803 and AGS) for comparison. We applied molecular and cellular techniques to measure cell survival and mRNA expression, investigated clinical data in the consensus of The Cancer Genome Atlas, and utilized high-throughput sequencing in MGC-803 cells and AGS cells for global gene expression analysis in inhibiting BRD9 conditions. Results Our studies showed that cancer cells with BRD9 overexpression, MGC-803 cells, were more sensitive to BRD9 inhibitors (i.e., BI9564 or BI7273) than AGS cells. The mechanism of BRD9 was related to the regulation of calcium voltage-gated channel auxiliary subunit alpha2 delta 4 (CANA2D4), calmodulin-like 6 (CALML6), guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O (GNAO1) and Potassium Inwardly Rectifying Channel Subfamily J, Member 5 (KCNJ5) oncogenes in the oxytocin signaling pathway. BRD9 inhibitors could enhance the sensitivity of gastric cancer MGC-803 cells to adriamycin and cisplatin, so we may reduce the dosage of chemotherapeutic agents in curing gastric cancers with BRD9 over expression by combining BI9564 or BI7273 with adriamycin or cisplatin. Conclusions Our study elucidated the feasibility and effectiveness of inhibiting BRD9 to reduce the adverse effects of first-line chemotherapeutic agents in treating gastric cancer with BRD9 overexpression. This study provides a scientific theoretical basis for a chemotherapy regimen in gastric cancer with BRD9 overexpression.

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Section: Discussionmentioning

confidence: 99%

BRD9 controls the oxytocin signaling pathway in gastric cancer via CANA2D4, CALML6, GNAO1, and KCNJ5

Wang¹,

Jiang²,

Yu³

2020

Transl Cancer Res TCR

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“…In addition, local tissue concentrations of oxytocin may give results of particular relevance to understanding the beneficial effects of this peptide. For example, within the microenvironment of ovarian tumors, oxytocin levels were measured at 200 times higher than those in plasma (Cuneo et al, 2019). These high levels of oxytocin may reflect a response to the tumor with apparent benefits to reducing inflammation.…”

Section: A Oxytocin Is Difficult To Assaymentioning

confidence: 97%

“…Levels of oxytocin measured within tumors were associated with inflammatory markers, including IL-6, as well as patient survival. Thus, tissues challenged by cancer may produce healing levels of oxytocin (Cuneo et al, 2019).…”

Section: B Oxytocin and Cancer: A Complex Relationshipmentioning

confidence: 99%

“…In addition to its protective role for developing and adult gastrointestinal tissue, endogenous oxytocin, at high levels, has been implicated in human wound healing ( Gouin et al, 2010 ) and is protective against cardiovascular dysfunction via a suppression of inflammatory processes mediated by neutrophils, macrophages, T lymphocytes, TNF- α , and IL-6 ( Jankowski et al, 2016 ; Reiss et al, 2019 ). Among other commonly studied models in which oxytocin has been shown to be anti-inflammatory are those involving the healing of tissue flaps ( Xu et al, 2017 ) and ovarian cancer ( Cuneo et al, 2019 ). Within human patients, higher levels of ascites oxytocin were associated with lower levels of the proinflammatory cytokine IL-6 and a significant survival advantage.…”

Section: Immunologic and Anti-inflammatory Effects Of Oxytocinmentioning

confidence: 99%

“…Within human patients, higher levels of ascites oxytocin were associated with lower levels of the proinflammatory cytokine IL-6 and a significant survival advantage. Moreover, oxytocin inhibited IL-6 production in cancer cell lines ( Cuneo et al, 2019 ). Oxytocin also may restore tissue after procedures that damage the nervous system, intestines, and cardiovascular system ( Karelina and DeVries, 2011 ; Bordt et al, 2019 ; Kingsbury and Bilbo, 2019 ).…”

Section: Immunologic and Anti-inflammatory Effects Of Oxytocinmentioning

confidence: 99%

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Is Oxytocin “Nature’s Medicine”?

et al. 2020

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Friend and foe: the regulation network of ascites components in ovarian cancer progression

Geng

Pan

et al. 2022

J. Cell Commun. Signal.

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The tumor microenvironment (TME) and its complex role in cancer progression have been hotspots of cancer research in recent years. Ascites, which occurs frequently in patients with ovarian cancer especially in advanced stages, represents a unique TME. Malignant ascites contains abundant cellular and acellular components that play important roles in tumorigenesis, growth, metastasis, and chemoresistance of ovarian cancer through complex molecular mechanisms and signaling pathways. As a valuable liquid biopsy sample, ascites fluid is also of great significance for the prognostic analysis of ovarian cancer. The components of ovarian cancer ascites are generally considered to comprise tumor-promoting factors; however, in recent years studies have found that ascites also contains tumor-suppressing factors, raising new perspectives on interactions between ascites and tumors. Malignant ascites directly constitutes the ovarian cancer microenvironment, therefore, the study of its components will aid in the development of new therapeutic strategies. This article reviews the current research on tumor-promoting and tumor-suppressing factors and molecular mechanisms of their actions in ovarian cancer-derived ascites and therapeutic strategies targeting ascites, which may provide references for the development of novel therapeutic targets for ovarian cancer in the future.

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

Cited by 14 publications

References 33 publications

BRD9 controls the oxytocin signaling pathway in gastric cancer via CANA2D4, CALML6, GNAO1, and KCNJ5

BRD9 controls the oxytocin signaling pathway in gastric cancer via CANA2D4, CALML6, GNAO1, and KCNJ5

Is Oxytocin “Nature’s Medicine”?

Friend and foe: the regulation network of ascites components in ovarian cancer progression

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