TY - T1的机械通风促进肺肿瘤由调制胆固醇细胞传播内容JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.01470 -2021欧元六世- 60 - 1 SP - 2101470 AU Ines Lopez-Alonso AU -塞西莉亚Lopez-Martinez盟宝拉Martin-Vicente Adrian Gonzalez-Lopez AU -劳拉Amado-Rodriguez盟盟-胡安Mayordomo-Colunga AU -塞西莉亚del Busto AU -滨伯纳尔非盟-艾琳克雷斯波盟极光Astudillo AU -米盖尔Arias-Guillen盟安东尼奥Fueyo Jorge Otero AU -艾萨克Almendros盟盟-赫Sanz-Fraile盟Ramon Farre盟吉列尔莫·m·Albaiceta Y1 - 2022/07/01 UR - //www.qdcxjkg.com/content/60/1/2101470.abstract N2 -背景机械的癌细胞可以改变他们的侵袭性。机械通气期间,肺可能暴露在增加数量的延伸,但结果尚未探索肺肿瘤。方法描述机械通风的影响在肺肿瘤的行为,侵袭性化验和转录组分析在癌症细胞系培养在静态条件或循环拉伸。黑色素瘤小鼠窝藏肺移植被提交给机械通风和转移性传播评估。额外的体内实验来确定mechanodependent特异性的反应。转移的发生率在一群研究肺癌患者接受机械通气与一组匹配的nonventilated病人。结果伸展增加侵袭性黑色素瘤B16F10luc2和肺腺癌A549细胞。我们确定了mechanosensitive upregulation通路参与胆固醇处理体外,导致增加pro-protein转化酶枯草杆菌蛋白酶/可馨类型9 (PCSK9)和LDLR表达,减少细胞内胆固醇和保护细胞刚度。的机械通风窝藏黑色素瘤小鼠植入大脑和肾脏转移增加2周后。PCSK9的封锁使用单克隆抗体细胞胆固醇和增加刚度和降低体内细胞体外侵袭性和转移。患者机械通气增加PCSK9丰富在肺肿瘤和转移的发生率,从而减少生存。Conclusions Our results suggest that mechanical stretch promote invasiveness of cancer cells, which may have clinically relevant consequences. Pharmacological manipulation of cholesterol endocytosis could be a novel therapeutic target in this setting.Even a short course of mechanical ventilation, such as during major surgery, promotes lung cancer dissemination. A mechanodependent modulation of cholesterol intake regulates cancer cell stiffness and could be a new therapeutic target in this setting. https://bit.ly/3G0IbcI ER -