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《工程(英文)》 >> 2021年 第7卷 第10期 doi: 10.1016/j.eng.2020.08.013

外泌体CD44与整合素α6β4结合激活宿主细胞重塑肿瘤微环境促进胰腺癌恶性转移

a Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
b CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai 200031, China
c National Research Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China

收稿日期: 2020-04-10 修回日期: 2020-07-20 录用日期: 2020-08-10 发布日期: 2020-10-08

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摘要

绝大多数胰腺癌患者的死亡都是由于癌细胞迅速转移到肺、肝、脑等重要器官造成的。其中,胰腺癌肝转移是胰腺癌患者死亡率高的原因之一。来自胰腺癌细胞的外泌体通常富含跨膜蛋白,用于支持肿瘤微环境的重编程和远处转移性病变的进展。我们的研究发现,由外泌体传递的跨膜糖蛋白CD44通过重编程肿瘤微环境,参与了胰腺癌的转移过程。CD44与整合素α6β4相互作用形成复合物,激活细胞内骨架蛋白及其信号通路,进而调控Src和Ras信号级联反应,促进肿瘤细胞的运动。值得注意的是,我们还证明了CD44-α6β4复合物可以通过外泌体的旁分泌作用传递到靶区。肝细胞选择性摄取具有高表达CD44的肿瘤外泌体,并通过刺激细胞因子、促炎因子和生长因子产生转移前生态位,最终支持肿瘤转移。我们的研究结果表明,外泌体CD44有可能作为胰腺癌临床诊断和治疗的生物标志物。

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