title: Reduced NADPH oxidase type 2 activity mediates sleep fragmentation-induced effects on TC1 tumors in mice.
abstract: The molecular mechanisms underlying how sleep fragmentation (SF) influences cancer growth and progression remain largely elusive. Here, we present evidence that SF reduced ROS production by downregulatinggp91phoxexpression and activity in TC1 cell tumor associated macrophages (TAMs), while genetic ablation of phagocytic Nox2 activity increased tumor cell proliferation, motility, invasion, and extravasationin vitro. Importantly, thein vivostudies using immunocompetent syngeneic murine tumor models suggested that Nox2 deficiency mimics SF-induced TAMs infiltration and subsequent tumor growth and invasion. Taken together, these studies reveal that perturbed sleep could adversely affect innate immunity within the tumor by altering Nox2 expression and activity, and indicate that selective potentiation of Nox2 activity may present a novel therapeutic strategy in the treatment of cancer.
authors.affiliation: Section of Pediatric Sleep Medicine; Department of Pediatrics; Pritzker School of Medicine; Biological Sciences Division; The University of Chicago ; Chicago, Illinois, USA.
authors.forename: Jiamao
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Section of Pediatric Sleep Medicine; Department of Pediatrics; Pritzker School of Medicine; Biological Sciences Division; The University of Chicago ; Chicago, Illinois, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Almendros
authors.affiliation: Section of Pediatric Sleep Medicine; Department of Pediatrics; Pritzker School of Medicine; Biological Sciences Division; The University of Chicago ; Chicago, Illinois, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Section of Pediatric Sleep Medicine; Department of Pediatrics; Pritzker School of Medicine; Biological Sciences Division; The University of Chicago ; Chicago, Illinois, USA.
authors.forename: Shelley X
authors.initials: SX
authors.lastname: Zhang
authors.affiliation: Section of Pediatric Sleep Medicine; Department of Pediatrics; Pritzker School of Medicine; Biological Sciences Division; The University of Chicago ; Chicago, Illinois, USA.
authors.forename: Alba
authors.initials: A
authors.lastname: Carreras
authors.affiliation: Section of Pediatric Sleep Medicine; Department of Pediatrics; Pritzker School of Medicine; Biological Sciences Division; The University of Chicago ; Chicago, Illinois, USA.
authors.forename: Zhuanhong
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Section of Pediatric Sleep Medicine; Department of Pediatrics; Pritzker School of Medicine; Biological Sciences Division; The University of Chicago ; Chicago, Illinois, USA.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
keywords: ANOVA, Analysis of variance; FBS, fetal bovine serum; HEPES, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; MFI, median fluorescence intensities; NADPH oxidase; Nox2, NADPH Oxidase Type 2; PMA, phorbol 12-myristate 13-acetate; ROS, reactive oxygen species; SE, standard error; SF, sleep fragmentation; TAMs, tumor associated macrophages; TLR-4, toll like receptor 4; WT, wild type; cancer; reactive oxygen species; rpm, revolutions per minute; sleep apnea; tumor associated macrophage