文章目录

中性粒细胞氧化应激介导肥胖相关血管功能障碍和转移性转移

原文发布日期：2021-05-03

英文摘要：

摘要翻译：

原文链接：

文章：

中性粒细胞氧化应激介导肥胖相关血管功能障碍和转移性转移

Neutrophil oxidative stress mediates obesity-associated vascular dysfunction and metastatic transmigration

原文发布日期：2021-05-03

英文摘要：

Metastasis is the leading cause of cancer-related deaths, and obesity is associated with increased breast cancer (BC) metastasis. Preclinical studies have shown that obese adipose tissue induces lung neutrophilia associated with enhanced BC metastasis to this site. Here we show that obesity leads to neutrophil-dependent impairment of vascular integrity through loss of endothelial adhesions, enabling cancer cell extravasation into the lung. Mechanistically, neutrophil-produced reactive oxygen species in obese mice increase neutrophil extracellular DNA traps (NETs) and weaken endothelial junctions, facilitating the influx of tumor cells from the peripheral circulation. In vivo treatment with catalase, NET inhibitors or genetic deletion of Nos2 reversed this effect in preclinical models of obesity. Imaging mass cytometry of lung metastasis samples from patients with cancer revealed an enrichment in neutrophils with low catalase levels correlating with elevated body mass index. Our data provide insights into potentially targetable mechanisms that underlie the progression of BC in the obese population.

摘要翻译：

转移是癌症致死的主要原因，而肥胖与乳腺癌（BC）转移增加相关。非olas实验研究表明，超重脂肪组织诱导肺中性粒细胞增多，增强乳腺癌转移至此处。我们在此展示了，肥胖导致依赖中性粒细胞的血管完整性受损通过端皮层粘附丢失，允许癌症细胞外移入肺部。机制上，肥胖小鼠产生反应性氧物种（ROS）增加中性粒细胞外分泌DNA陷阱（NETs）并减弱端皮质细胞间结合，促进肿瘤细胞从循环进入肺部。体内用过氧化氢酶抑制剂、NET抑制剂或 Nos2基因的遗传删除逆转了这种影响。将 imaging mass cytometry应用于患者癌症组 lung metastasis样本的影像分析，显示出低过氧化氢酶水平的中性粒细胞的富集，并且与体重指数升高相关。我们得出的数据提供了一种潜在的可靶向机制的见解，这些机制有助于理解肥胖人群BC进展。