Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
Department of Biochemistry, College of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Radiat Res. 2020 Jul 8;194(1):71-80. doi: 10.1667/RR15555.1.
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.
大量研究表明，外泌体在肿瘤生物学发展中发挥着重要作用。然而，在照射后不同氧条件下，外泌体蛋白在癌症进展中的功能仍知之甚少。在这项研究中，非小细胞肺癌（NSCLC）A549 细胞在常氧或低氧条件下接受 γ 射线照射，然后收集照射细胞释放的外泌体，并与未照射的 A549 细胞或人脐静脉内皮细胞（HUVEC）共培养。结果发现，外泌体显著促进了 A549 细胞的增殖、迁移和侵袭，以及 HUVEC 的增殖和血管生成。此外，与来自常氧细胞的外泌体相比，来自低氧细胞和/或照射细胞的外泌体在肿瘤进展中具有更强的驱动力。同时，使用串联质量标签（TMT）检测了来自不同条件下 A549 细胞的外泌体中的蛋白质，并分析了它们的表达谱。结果发现，血管生成素样蛋白 4（ANGPTL4）的外泌体衍生蛋白促进了 A549 细胞的迁移以及 HUVEC 的血管生成，表明其作为转移的有效诊断生物标志物甚至是肺癌的治疗靶点的潜力。
