Myeloid cell-derived HOCl is a paracrine effector that trans-inhibits IKK/NF-κB in melanoma cells and limits early tumor progression.

ABSTRACT: The myeloperoxidase (MPO) system of myeloid-derived cells (MDCs) is central to cellular innate immunity. Upon MDC activation, MPO is secreted into phagosomes where it catalyzes the production of hypochlorous acid (HOCl), a potent chlorinating oxidant. Here, we demonstrated that the myeloid lineage-restricted MPO-HOCl system had antitumor effects in early melanoma growth in aged mice. Orthotopic melanomas grew more slowly in immunocompetent MPO^+/+ host mice compared to age-matched syngeneic MPO^-/- mice. Real-time intravital tumor imaging in vivo and in cell cocultures revealed a cell-cell proximity-dependent association between MDC-derived MPO enzyme activity and blockade of ligand-induced IκBα degradation in tumor cells. HOCl directly trans-inhibited IκB

SUBMITTER: Liu TW 

PROVIDER: S-EPMC12506183 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature