Inducible nitric oxide synthase-derived extracellular nitric oxide flux regulates proinflammatory responses at the single cell level.

ABSTRACT: The role of nitric oxide (NO) in cancer progression has largely been studied in the context of tumor NOS2 expression. However, pro- versus anti-tumor signaling is also affected by tumor cell-macrophage interactions. While these cell-cell interactions are partly regulated by NO, the functional effects of NO flux on proinflammatory (M1) macrophages are unknown. Using a triple negative murine breast cancer model, we explored the potential role of macrophage Nos2 on 4T1 tumor progression. The effects of NO on macrophage phenotype were examined in bone marrow derived macrophages from wild type and Nos2^-/- mice following in vitro stimulation with cytokine/LPS combinations to produce low, medium, and high NO flux. Remarkably, Nos2 induction was spatially distinct, where Nos2^high</

SUBMITTER: Somasundaram V 

PROVIDER: S-EPMC6920088 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature