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Effects of Hypoxia and Radiation-Induced Exosomes on Migration of Lung Cancer Cells and Angiogenesis of Umbilical Vein Endothelial Cells.
Radiation Research ( IF 2.5 ) Pub Date : 2020-07-08 , DOI: 10.1667/rr15555.1
Fang Mo 1 , Yanwu Xu 2 , Junling Zhang 1 , Lin Zhu 1 , Chen Wang 1 , Xiaofei Chu 1 , Yan Pan 1 , Yang Bai 1 , Chunlin Shao 1 , Jianghong Zhang 1
Affiliation  

Numerous studies have shown that exosomes play important roles in tumor biology development. However, the function of exosomal protein in cancer progression under different oxygen condition after irradiation is poorly understood. In this study, non-small cell lung cancer (NSCLC) A549 cells were γ-ray irradiated under normoxic or hypoxic conditions, then the exosomes released from the irradiated cells were collected and co-cultured with nonirradiated A549 cells or human umbilical vein endothelial cells (HUVECs). It was found that the exosomes significantly promoted the proliferation, migration and invasion of A549 cells as well as the proliferation and angiogenesis of HUVECs. Moreover, the exosomes released from hypoxic cells and/or irradiated cells had more powerful driving force in tumor progression compared to that generated from normoxia cells. Meanwhile, the proteins contained in the exosomes derived from A549 cells under different conditions were detected using tandem mass tag (TMT), and their expression profiles were analyzed. It was found that the exosome-derived protein of angiopoietin-like 4 (ANGPTL4) contributed to the migration of A549 cells as well as the angiogenesis of HUVECs, suggesting its potential as an effective diagnostic biomarker of metastasis and even a therapeutic target of lung cancer.

中文翻译:

低氧和辐射诱导的外来体对肺癌细胞迁移和脐静脉内皮细胞血管生成的影响。

大量研究表明,外泌体在肿瘤生物学发展中起重要作用。然而,人们对外体蛋白在辐射后不同氧气条件下癌症进展中的功能了解甚少。在这项研究中,在常氧或低氧条件下对非小细胞肺癌(NSCLC)A549细胞进行γ射线辐照,然后收集从辐照细胞释放的外泌体,并与未辐照的A549细胞或人脐静脉内皮细胞共培养(HUVEC)。发现外泌体显着促进了A549细胞的增殖,迁移和侵袭以及HUVEC的增殖和血管生成。而且,与正常氧细胞产生的外泌体相比,低氧细胞和/或受辐照细胞释放的外泌体在肿瘤进展中具有更强大的驱动力。同时,使用串联质量标签(TMT)检测在不同条件下来自A549细胞的外泌体中所含的蛋白质,并分析其表达谱。已发现,血管生成素样蛋白4(ANGPTL4)的外体衍生蛋白促进了A549细胞的迁移以及HUVEC的血管生成,表明其具有作为转移的有效诊断生物标志物甚至是肺癌治疗靶点的潜力。 。
更新日期:2020-04-30
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