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

Autor: Flaherty RL; School of Pharmacy and Biomolecular Sciences, University of Brighton, Centre for Stress and Age-related Disease, Moulsecoomb, Brighton, BN2 4GJ, UK., Intabli H; School of Pharmacy and Biomolecular Sciences, University of Brighton, Centre for Stress and Age-related Disease, Moulsecoomb, Brighton, BN2 4GJ, UK., Falcinelli M; School of Pharmacy and Biomolecular Sciences, University of Brighton, Centre for Stress and Age-related Disease, Moulsecoomb, Brighton, BN2 4GJ, UK., Bucca G; School of Pharmacy and Biomolecular Sciences, University of Brighton, Centre for Stress and Age-related Disease, Moulsecoomb, Brighton, BN2 4GJ, UK., Hesketh A; School of Pharmacy and Biomolecular Sciences, University of Brighton, Centre for Stress and Age-related Disease, Moulsecoomb, Brighton, BN2 4GJ, UK., Patel BA; School of Pharmacy and Biomolecular Sciences, University of Brighton, Centre for Stress and Age-related Disease, Moulsecoomb, Brighton, BN2 4GJ, UK., Allen MC; School of Pharmacy and Biomolecular Sciences, University of Brighton, Centre for Stress and Age-related Disease, Moulsecoomb, Brighton, BN2 4GJ, UK., Smith CP; School of Pharmacy and Biomolecular Sciences, University of Brighton, Centre for Stress and Age-related Disease, Moulsecoomb, Brighton, BN2 4GJ, UK., Flint MS; School of Pharmacy and Biomolecular Sciences, University of Brighton, Centre for Stress and Age-related Disease, Moulsecoomb, Brighton, BN2 4GJ, UK. Electronic address: m.flint@brighton.ac.uk.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2019 Sep 10; Vol. 459, pp. 59-71. Date of Electronic Publication: 2019 May 24.
DOI: 10.1016/j.canlet.2019.05.027
Abstrakt: 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.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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