Zheng Jiamao, Almendros Isaac, Wang Yang, Zhang Shelley X, Carreras Alba, Qiao Zhuanhong, Gozal David
Section of Pediatric Sleep Medicine; Department of Pediatrics; Pritzker School of Medicine; Biological Sciences Division; The University of Chicago ; Chicago, Illinois, USA.
Oncoimmunology. 2015 Mar 6;4(2):e976057. doi: 10.4161/2162402X.2014.976057. eCollection 2015 Feb.
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 downregulating expression and activity in TC1 cell tumor associated macrophages (TAMs), while genetic ablation of phagocytic Nox2 activity increased tumor cell proliferation, motility, invasion, and extravasation . Importantly, the studies 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.
睡眠碎片化（SF）影响癌症生长和进展的分子机制在很大程度上仍不清楚。在此，我们提供证据表明，SF通过下调TC1细胞肿瘤相关巨噬细胞（TAM）中的表达和活性来减少ROS产生，而吞噬性Nox2活性的基因消融增加了肿瘤细胞的增殖、运动、侵袭和外渗。重要的是，使用具有免疫活性的同基因小鼠肿瘤模型的研究表明，Nox2缺乏模拟了SF诱导的TAM浸润以及随后的肿瘤生长和侵袭。综上所述，这些研究揭示了睡眠紊乱可能通过改变Nox2表达和活性对肿瘤内的固有免疫产生不利影响，并表明选择性增强Nox2活性可能是治疗癌症的一种新的治疗策略。
