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癌细胞通过细胞外囊泡复制迁移行为并交换信号网络。

Cancer cells copy migratory behavior and exchange signaling networks via extracellular vesicles.

机构信息

Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Oncode Institute, Hubrecht Institute-KNAW & University Medical Centre Utrecht, Utrecht, The Netherlands.

出版信息

EMBO J. 2018 Aug 1;37(15). doi: 10.15252/embj.201798357. Epub 2018 Jun 14.

DOI:10.15252/embj.201798357
PMID:29907695
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6068466/
Abstract

Recent data showed that cancer cells from different tumor subtypes with distinct metastatic potential influence each other's metastatic behavior by exchanging biomolecules through extracellular vesicles (EVs). However, it is debated how small amounts of cargo can mediate this effect, especially in tumors where all cells are from one subtype, and only subtle molecular differences drive metastatic heterogeneity. To study this, we have characterized the content of EVs shed by two clones of melanoma (B16) tumors with distinct metastatic potential. Using the Cre-LoxP system and intravital microscopy, we show that cells from these distinct clones phenocopy their migratory behavior through EV exchange. By tandem mass spectrometry and RNA sequencing, we show that EVs shed by these clones into the tumor microenvironment contain thousands of different proteins and RNAs, and many of these biomolecules are from interconnected signaling networks involved in cellular processes such as migration. Thus, EVs contain numerous proteins and RNAs and act on recipient cells by invoking a multi-faceted biological response including cell migration.

摘要

最近的数据表明，不同转移潜能肿瘤亚型的癌细胞通过细胞外囊泡（EVs）交换生物分子，从而影响彼此的转移行为。然而，对于这种影响如何通过少量货物来介导，特别是在所有细胞均来自单一亚型的肿瘤中，仅微小的分子差异就会驱动转移异质性，目前仍存在争议。为了研究这一点，我们对两种具有不同转移潜能的黑色素瘤（B16）肿瘤克隆分泌的 EV 的内容进行了表征。我们使用 Cre-LoxP 系统和活体显微镜，显示这些不同克隆的细胞通过 EV 交换模拟其迁移行为。通过串联质谱和 RNA 测序，我们表明这些克隆在肿瘤微环境中分泌的 EV 中含有数千种不同的蛋白质和 RNA，其中许多生物分子来自相互连接的信号网络，这些信号网络参与细胞迁移等细胞过程。因此，EV 包含许多蛋白质和 RNA，并通过引发包括细胞迁移在内的多方面生物学反应来作用于受体细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/3cedb27e9943/EMBJ-37-e98357-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/72e2222be7f1/EMBJ-37-e98357-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/f8d342d6c9fd/EMBJ-37-e98357-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/470feec2021c/EMBJ-37-e98357-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/bd36ef68684b/EMBJ-37-e98357-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/7c356d9dca74/EMBJ-37-e98357-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/2706cec6f998/EMBJ-37-e98357-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/5664e9f6b1ef/EMBJ-37-e98357-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/952a8d3f2239/EMBJ-37-e98357-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/a6181eda425d/EMBJ-37-e98357-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/180a9714fb23/EMBJ-37-e98357-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/4af923932779/EMBJ-37-e98357-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/3cedb27e9943/EMBJ-37-e98357-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/72e2222be7f1/EMBJ-37-e98357-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/f8d342d6c9fd/EMBJ-37-e98357-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/470feec2021c/EMBJ-37-e98357-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/bd36ef68684b/EMBJ-37-e98357-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/7c356d9dca74/EMBJ-37-e98357-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/2706cec6f998/EMBJ-37-e98357-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/5664e9f6b1ef/EMBJ-37-e98357-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/952a8d3f2239/EMBJ-37-e98357-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/a6181eda425d/EMBJ-37-e98357-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/180a9714fb23/EMBJ-37-e98357-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/4af923932779/EMBJ-37-e98357-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa99/6068466/3cedb27e9943/EMBJ-37-e98357-g012.jpg

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