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 language | English |
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Pages (from-to) | 59-71 |
Number of pages | 13 |
Journal | Cancer Letters |
Volume | 459 |
DOIs | |
Publication status | Published - 24 May 2019 |
Keywords
- glucorticoids
- breast cancer
- Glucocorticoids
- Breast cancer
- Stress
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Melanie Flint
- School of Applied Sciences - Professor of Stress and Cancer Research
- Centre for Lifelong Health
Person: Academic
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Bhavik Patel
- School of Applied Sciences - Prof. Clinical and Bioanalytical Chemistry
- Applied Chemical Sciences Research Excellence Group
- Centre for Lifelong Health
Person: Academic