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乳腺癌细胞释放的外泌体刺激细胞运动。

Exosomes released from breast cancer carcinomas stimulate cell movement.

作者信息

Harris Dinari A, Patel Sajni H, Gucek Marjan, Hendrix An, Westbroek Wendy, Taraska Justin W

机构信息

Laboratory of Molecular Biophysics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

Proteomics Core Facility, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

出版信息

PLoS One. 2015 Mar 23;10(3):e0117495. doi: 10.1371/journal.pone.0117495. eCollection 2015.

Abstract

For metastasis to occur cells must communicate with to their local environment to initiate growth and invasion. Exosomes have emerged as an important mediator of cell-to-cell signalling through the transfer of molecules such as mRNAs, microRNAs, and proteins between cells. Exosomes have been proposed to act as regulators of cancer progression. Here, we study the effect of exosomes on cell migration, an important step in metastasis. We performed cell migration assays, endocytosis assays, and exosome proteomic profiling on exosomes released from three breast cancer cell lines that model progressive stages of metastasis. Results from these experiments suggest: (1) exosomes promote cell migration and (2) the signal is stronger from exosomes isolated from cells with higher metastatic potentials; (3) exosomes are endocytosed at the same rate regardless of the cell type; (4) exosomes released from cells show differential enrichment of proteins with unique protein signatures of both identity and abundance. We conclude that breast cancer cells of increasing metastatic potential secrete exosomes with distinct protein signatures that proportionally increase cell movement and suggest that released exosomes could play an active role in metastasis.

摘要

为了发生转移,细胞必须与它们的局部环境进行沟通,以启动生长和侵袭。外泌体已成为细胞间信号传导的重要介质,通过在细胞之间传递mRNA、微小RNA和蛋白质等分子来实现。外泌体被认为是癌症进展的调节因子。在这里,我们研究外泌体对细胞迁移的影响,细胞迁移是转移过程中的一个重要步骤。我们对三种模拟转移进展阶段的乳腺癌细胞系释放的外泌体进行了细胞迁移试验、内吞试验和外泌体蛋白质组分析。这些实验结果表明:(1)外泌体促进细胞迁移;(2)从具有较高转移潜能的细胞中分离出的外泌体发出的信号更强;(3)无论细胞类型如何,外泌体的内吞速率相同;(4)从细胞中释放的外泌体显示出蛋白质的差异富集,具有独特的蛋白质特征,包括身份和丰度。我们得出结论,转移潜能增加的乳腺癌细胞分泌具有独特蛋白质特征的外泌体,这些外泌体按比例增加细胞运动,并表明释放的外泌体可能在转移中发挥积极作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca03/4370373/335582dfe442/pone.0117495.g001.jpg

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