Exosome cargo reflects TGF-β1-mediated epithelial-to-mesenchymal transition (EMT) status in A549 human lung adenocarcinoma cells

Exosome cargo reflects TGF-β1-mediated epithelial-to-mesenchymal transition (EMT) status in A549 human lung adenocarcinoma cells
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DOI:
10.1016/j.bbrc.2016.07.124
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发表时间:
2016-09-16
影响因子:
3.1
通讯作者:
Kim, Soon Ae
Kim, Soon Ae
中科院分区:
生物学4区
文献类型:
--
作者:
Kim, Jiyeon;Kim, Tae Yeon;Kim, Soon Ae

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肿瘤细胞分泌外泌体改变局部微环境,进而促进细胞间通讯和转移。虽然来源于癌细胞的外泌体可能有助于未转化细胞中的上皮间质转化(EMT),但很少有研究在诱导EMT时定义外泌体货物。在这项研究中,我们研究了外泌体货物的变化,从上皮间充质细胞表型诱导EMT与转化生长因子(TGF)-β 1在A549人肺腺癌细胞。外泌体的蛋白质含量反映了细胞表型的变化。此外,miR-23 a在间充质转化后的外泌体中显著富集。在通过用TGF-β 1对上皮细胞类型的EMT诱导处理来自间充质细胞的外来体后,观察到蛋白质表达水平和细胞形态的表型变化。外泌体的自体处理增强了fl-catenin的转录活性和丰度。我们的研究结果表明,外泌体蛋白和miRNA含量反映了其来源的生理条件,外泌体通过自分泌信号诱导表型变化。(C)2016 Elsevier Inc. All rights reserved.
It has been suggested that tumor cells secrete exosomes to modify the local microenvironment, which then promotes intercellular communication and metastasis. Although exosomes derived from cancer cells may contribute to the epithelial mesenchymal transition (EMT) in untransformed cells, few studies have defined exosome cargo upon induction of EMT. In this study, we investigated the changes in exosomal cargo from the epithelial to mesenchymal cell phenotype by inducing EMT with transforming growth factor (TGF)-beta 1 in A549 human lung adenocarcinoma cells. The protein content of the exosomes reflects the change in the cell phenotype. In addition, miR-23a was significantly enriched in the exosomes after mesenchymal transition. Following treatment of exosomes from mesenchymal cells via EMT induction with TGF-beta 1 to the epithelial cell type, phenotypic changes in protein expression level and cell morphology were observed. Autologous treatment of exosomes enhanced the transcriptional activity and abundance of fl-catenin. Our results suggest that the exosomal protein and miRNA content reflects the physiological condition of its source and that exosomes induce phenotypic changes via autocrine signaling. (C) 2016 Elsevier Inc. All rights reserved.