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Exosomal Leucine-Rich-Alpha2-Glycoprotein 1 Derived from Non-Small-Cell Lung Cancer Cells Promotes Angiogenesis via TGF-β Signal Pathway
Molecular Therapy: Oncology ( IF 5.3 ) Pub Date : 2019-08-07 , DOI: 10.1016/j.omto.2019.08.001
Zifan Li , Chao Zeng , Qiaohong Nong , Feihu Long , Jixian Liu , Zhimin Mu , Baokun Chen , Da Wu , Hao Wu

Non-small-cell lung cancer (NSCLC) is a major cause for cancer-related deaths around the globe, partially due to the frequent recurrence and metastasis. Leucine-rich-alpha2-glycoprotein 1 (LRG1) is reportedly upregulated in several cancers including NSCLC; however, its functions in NSCLC remain elusive. We used quantitative real-time PCR and western blot assays to evaluate the expression patterns of LRG1 in tumor tissues collected from NSCLC patients, as well as NSCLC cell lines, and examined the effects of LRG1 on the proliferation, migration, and invasion of NSCLC cells. Further, we isolated exosomes from the blood of NSCLC patients, as well as NSCLC cell cultures, and assessed the impact of exosome exposure on the angiogenic capacities of human umbilical vein endothelial cells. LRG1 was upregulated in NSCLC tissues and cells and induced an enhancement of NSCLC cell proliferation, migration, and invasion. In addition, LRG1 was enriched in the exosomes derived from NSCLC tissue and cells, and mediated a proangiogenic effect via the activation of transforming growth factor β (TGF-β) pathway. Exosomal LRG1 derived from NSCLC cells promotes angiogenesis via TGF-β signaling and possesses the potential of a therapeutic target in NSCLC treatment.



中文翻译:

来源于非小细胞肺癌细胞的外泌体富亮氨酸α2糖蛋白1通过TGF-β信号通路促进血管生成

非小细胞肺癌(NSCLC)是导致全球癌症相关死亡的主要原因,部分原因是其频繁复发和转移。据报道,富含亮氨酸的α2-糖蛋白1(LRG1)在包括NSCLC在内的多种癌症中上调。但是,它在NSCLC中的功能仍然难以捉摸。我们使用实时荧光定量PCR和Western印迹分析来评估LRG1在从NSCLC患者以及NSCLC细胞系收集的肿瘤组织中的表达模式,并研究了LRG1对NSCLC细胞增殖,迁移和侵袭的影响。此外,我们从NSCLC患者的血液以及NSCLC细胞培养物中分离了外泌体,并评估了外泌体暴露对人脐静脉内皮细胞血管生成能力的影响。LRG1在NSCLC组织和细胞中上调,并诱导NSCLC细胞增殖,迁移和侵袭增强。此外,LRG1富含来自NSCLC组织和细胞的外泌体,并通过激活转化生长因子β(TGF-β)途径介导促血管生成作用。来源于NSCLC细胞的外泌体LRG1通过TGF-β信号传导促进血管生成,并具有在NSCLC治疗中作为治疗靶标的潜力。

更新日期:2019-08-07
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