Stress hormone-mediated acceleration of breast cancer metastasis is halted by inhibition of nitric oxide synthase

Renée L. Flaherty, Haya Intabli, Marta Falcinelli, Giselda Bucca, Andrew Hesketh, Bhavik Patel, Marcus Allen, Colin Smith, Melanie Flint

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Stress hormones have been shown to be important mediators in driving malignant growth and reducing treatment efficacy in breast cancer. Glucocorticoids can induce DNA damage through an inducible nitric oxide synthase (iNOS) mediated pathway to increase levels of nitric oxide (NO). Using an immune competent mouse breast cancer model and 66CL4 breast cancer cells we identified a novel role of NOS inhibition to reduce stress-induced breast cancer metastasis. On a mechanistic level we show that the glucocorticoid cortisol induces expression of keys genes associated with angiogenesis, as well as pro-tumourigenic immunomodulation. Transcriptomics analysis confirmed that in the lungs of tumour-bearing mice, stress significantly enriched pathways associated with tumourigenesis, some of which could be regulated with NOS inhibition. These results demonstrate the detrimental involvement of NOS in stress hormone signalling, and the potential future benefits of NOS inhibition in highly stressed patients.

Original languageEnglish
Pages (from-to)59-71
Number of pages13
JournalCancer Letters
Volume459
DOIs
Publication statusPublished - 24 May 2019

Fingerprint

Nitric Oxide Synthase
Hormones
Breast Neoplasms
Neoplasm Metastasis
Glucocorticoids
Bearings (structural)
Immunomodulation
Nitric Oxide Synthase Type II
DNA Damage
Hydrocortisone
Tumors
Nitric Oxide
Genes
Cells
Gene Expression
Lung
DNA
Growth
Neoplasms

Keywords

  • glucorticoids
  • breast cancer
  • Glucocorticoids
  • Breast cancer
  • Stress

Cite this

Flaherty, Renée L. ; Intabli, Haya ; Falcinelli, Marta ; Bucca, Giselda ; Hesketh, Andrew ; Patel, Bhavik ; Allen, Marcus ; Smith, Colin ; Flint, Melanie. / Stress hormone-mediated acceleration of breast cancer metastasis is halted by inhibition of nitric oxide synthase. In: Cancer Letters. 2019 ; Vol. 459. pp. 59-71.
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Stress hormone-mediated acceleration of breast cancer metastasis is halted by inhibition of nitric oxide synthase. / Flaherty, Renée L.; Intabli, Haya; Falcinelli, Marta; Bucca, Giselda; Hesketh, Andrew; Patel, Bhavik; Allen, Marcus; Smith, Colin; Flint, Melanie.

In: Cancer Letters, Vol. 459, 24.05.2019, p. 59-71.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Flaherty, Renée L.

AU - Intabli, Haya

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AU - Bucca, Giselda

AU - Hesketh, Andrew

AU - Patel, Bhavik

AU - Allen, Marcus

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