Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
ReviewThe role of nitric oxide in melanoma
Section snippets
Mechanisms of nitric oxide production in melanoma
Nitric oxide (NO) is a free radical inorganic signaling molecule that is generated via multiple mechanisms (Fig. 1). One of these mechanisms catalyzed by nitric oxide synthase (NOS) is the oxidation reaction of L-arginine and oxygen with a NADPH co-substrate to produce L-citrulline and NO [1]. There are 3 isotypes of NOS in humans: neuronal NOS (nNOS or NOS1), inducible NOS (iNOS or NOS2) and endothelial NOS (eNOS or NOS3). iNOS is transcriptionally induced by immunologic stimuli produced by
Conclusion
Although NO is primarily understood to be a gaseous signaling molecule, the evidence illustrates that NO has a multifaceted role in the development of melanoma. NO mediates effects through the melanoma cell itself, immune cell subsets (e.g. MDSC, DC, cytotoxic T cells, tumor associated macrophages), and the tumor microenvironment (e.g. vasculature, lymphatics). A dichotomy in this paper has been established in that NO can have both tumor promoting and inhibitory effects. Many of these effects
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Acknowledgements
J. Markowitz receives support from the Donald A Adam Comprehensive Melanoma Research Center at Moffitt Cancer Center and is also an Assistant Professor in the USF Morsani College of Medicine Department of Oncologic Sciences. The research was supported in part by the National Cancer Institute, part of the National Institutes of Health, Moffitt Skin Cancer SPORE (P50 CA168536). This work has been supported in part by the H. Lee Moffitt Cancer Center & Research Institute; an NCI designated
Conflicts of interest
The authors declare that they have no conflicts of interest.
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