Nitric oxide favours tumour-promoting inflammation through mitochondria-dependent and -independent actions on macrophages
Name:
35660630.pdf
Size:
9.145Mb
Format:
PDF
Description:
Identified with Open Access button
Authors
Drehmer, DaianaMesquita Luiz, J. P.
Hernandez, C. A. S.
Alves-Filho, J. C.
Hussell, T.
Townsend, Paul A
Moncada, Salvador
Affiliation
Division of Cancer Sciences, Manchester Cancer Research Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UKIssue Date
2022
Metadata
Show full item recordAbstract
Production of nitric oxide (NO) has been demonstrated in several malignancies, however its role remains not fully understood, specifically in relation to the metabolic and functional implications that it may have on immune cells participating in tumorigenesis. Here, we show that inducible NO synthase (iNOS) is expressed in cancers of the colon and the prostate, mainly by tumour cells, and NO generation is evidenced by widespread nitrotyrosine (NT) staining in tumour tissue. Furthermore, presence of NT is observed in the majority of tumour-associated macrophages (TAMs), despite low iNOS expression by these cells, suggesting that NO from the tumour microenvironment affects TAMs. Indeed, using a co-culture model, we demonstrate that NO produced by colon and prostate cancer cells is sufficient to induce NT formation in neighbouring macrophages. Moreover, exposure to exogenous NO promotes mitochondria-dependent and -independent changes in macrophages, which orientate their polarity towards an enhanced pro-inflammatory phenotype, whilst decreasing antigen-presenting function and wound healing capacity. Abrogating endogenous NO generation in murine macrophages, on the other hand, decreases their pro-inflammatory phenotype. These results suggest that the presence of NO in cancer may regulate TAM metabolism and function, favouring the persistence of inflammation, impairing healing and subverting adaptive immunity responses.Citation
Drehmer D, Mesquita Luiz JP, Hernandez CAS, Alves-Filho JC, Hussell T, Townsend PA, et al. Nitric oxide favours tumour-promoting inflammation through mitochondria-dependent and -independent actions on macrophages. Vol. 54, Redox Biology. Elsevier BV; 2022. p. 102350.Journal
Redox BiologyDOI
10.1016/j.redox.2022.102350PubMed ID
35660630Additional Links
https://dx.doi.org/10.1016/j.redox.2022.102350Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1016/j.redox.2022.102350