The effect of nitric oxide (NO) synthase (NOS) II expression on cancer biology is unclear and difficult to define, with multiple reports of pro- and anti-cancer actions. Here we address the major factors that seem likely to account for these paradoxical behaviors, which include variability in NO production, heterogeneity in NO chemistry (and thus its cellular actions), and differential cellular responses. In addition, we suggest that a major determinant of the outcome of NO actions in the tumor environment is cellular adaptation/selection to the cytotoxic actions of NO.
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Lancaster et al. (2006) studied this question.
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