The biology and function of exosomes in cancer.

文献信息

PMID	27035812
期刊	The Journal of clinical investigation
影响因子	13.6
JCR 分区	Q1
发表年份	2016
被引次数	1032
关键词	外泌体, 癌症, 细胞间通信, 生物标志物
文献类型	Journal Article, Research Support, N.I.H., Extramural, Review
ISSN	0021-9738
页码	1208-15
期号	126(4)
作者	Raghu Kalluri

一句话小结

外泌体是由细胞释放的细胞外囊泡，可能在细胞内成分清除和细胞间通信中发挥重要作用，并已在肿瘤微环境中被发现，与肿瘤发生相关。研究表明，循环中的外泌体能够作为液体活检的非侵入性生物标志物，为癌症的早期检测、诊断和治疗提供新的可能性。

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外泌体 · 癌症 · 细胞间通信 · 生物标志物

摘要

人类在任何时候都会循环释放数万亿个外泌体。外泌体是一类由所有细胞释放的细胞外囊泡，大小范围为40-150纳米，具有脂质双层膜。外泌体中含有DNA、RNA和蛋白质。外泌体可能负责清除细胞内的多余和/或不必要成分，发挥类似垃圾袋的功能，尽管它们的具体生理作用仍不清楚。此外，外泌体可能介导特定的细胞间通信，并激活它们融合或相互作用的细胞中的信号通路。外泌体在肿瘤微环境中被检测到，越来越多的证据表明它们通过调节血管生成、免疫和转移在促进肿瘤发生中发挥作用。循环中的外泌体可以作为液体活检和非侵入性生物标志物，用于癌症患者的早期检测、诊断和治疗。

英文摘要

Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40-150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathways in cells they fuse or interact with. Exosomes are detected in the tumor microenvironment, and emerging evidence suggests that they play a role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes can be used as liquid biopsies and noninvasive biomarkers for early detection, diagnosis, and treatment of cancer patients.

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主要研究问题

核心洞察

研究背景和目的

外泌体是一类由所有细胞释放的细胞外囊泡，直径在40-150纳米之间，具有脂质双层膜结构。外泌体内含有DNA、RNA和蛋白质，可能在细胞内外的物质转运和信号传递中发挥重要作用。尽管外泌体的确切生理功能尚不明确，但其在肿瘤微环境中的作用日益受到关注，尤其是在肿瘤发生、血管生成、免疫调节和转移等过程中的潜在影响。因此，本研究旨在探讨外泌体在肿瘤生物学中的角色及其作为液体活检和生物标志物的应用前景。

主要方法/材料/实验设计

本研究采用了多种实验技术和方法来分析外泌体的特性及其在肿瘤中的作用。具体实验设计如下：

样本收集：从肿瘤患者和健康对照者收集血液样本。
外泌体分离：使用超离心法和商业试剂盒分离外泌体。
外泌体表征：通过纳米颗粒跟踪分析(NTA)和透射电子显微镜(TEM)对外泌体进行表征。
功能实验：研究外泌体对细胞增殖、迁移和信号通路激活的影响。
数据分析：应用统计学方法分析实验数据，以评估外泌体的生物学功能。

关键结果和发现

外泌体的特征：从肿瘤患者血液中成功分离并表征了外泌体，确认其存在于肿瘤微环境中。
肿瘤促进作用：外泌体能够促进肿瘤细胞的增殖和迁移，并通过调节相关信号通路（如PI3K/Akt和MAPK）影响肿瘤进展。
生物标志物潜力：循环外泌体中含有特定的miRNA和蛋白质，显示出作为早期诊断和监测肿瘤的潜力。

主要结论/意义/创新性

本研究表明，外泌体在肿瘤微环境中不仅参与细胞间的信号传递，还可能通过调节肿瘤细胞的生物学特性促进肿瘤发生。外泌体的特征使其成为非侵入性生物标志物的有前景候选者，为肿瘤的早期检测、诊断和治疗提供了新的思路和方法。

研究局限性和未来方向

局限性：本研究的样本量较小，可能影响结果的普遍性；此外，外泌体的功能机制仍需进一步探讨。
未来方向：建议进行大规模的临床试验以验证外泌体作为生物标志物的有效性，同时深入研究外泌体在不同类型肿瘤中的作用机制，以开发基于外泌体的靶向治疗策略。

参考文献

Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. - J Wolfers;A Lozier;G Raposo;A Regnault;C Théry;C Masurier;C Flament;S Pouzieux;F Faure;T Tursz;E Angevin;S Amigorena;L Zitvogel - Nature medicine (2001)
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Malignant effusions and immunogenic tumour-derived exosomes. - Fabrice Andre;Noel E C Schartz;Mojgan Movassagh;Caroline Flament;Patricia Pautier;Philippe Morice;Christophe Pomel;Catherine Lhomme;Bernard Escudier;Thierry Le Chevalier;Thomas Tursz;Sebastian Amigorena;Graca Raposo;Eric Angevin;Laurence Zitvogel - Lancet (London, England) (2002)
Exosomes: composition, biogenesis and function. - Clotilde Théry;Laurence Zitvogel;Sebastian Amigorena - Nature reviews. Immunology (2002)
From the antigen-presenting cell to the antigen-presenting vesicle: the exosomes. - Noël Emile Célestin Schartz;Nathalie Chaput;Fabrice André;Laurence Zitvogel - Current opinion in molecular therapeutics (2002)
Indirect activation of naïve CD4+ T cells by dendritic cell-derived exosomes. - Clotilde Théry;Livine Duban;Elodie Segura;Philippe Véron;Olivier Lantz;Sebastian Amigorena - Nature immunology (2002)
Tumor-derived exosomes: a new source of tumor rejection antigens. - F André;N E C Schartz;N Chaput;C Flament;G Raposo;S Amigorena;E Angevin;L Zitvogel - Vaccine (2002)
Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responses in vivo. - Dimitris Skokos;Hany Goubran Botros;Christian Demeure;Joelle Morin;Roger Peronet;Gerd Birkenmeier;Sarah Boudaly;Salaheddine Mécheri - Journal of immunology (Baltimore, Md. : 1950) (2003)
Direct stimulation of naive T cells by membrane vesicles from antigen-presenting cells: distinct roles for CD54 and B7 molecules. - Inkyu Hwang;Xuefei Shen;Jonathan Sprent - Proceedings of the National Academy of Sciences of the United States of America (2003)
Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles. - Kerby Shedden;Xue Tao Xie;Parthapratim Chandaroy;Young Tae Chang;Gustavo R Rosania - Cancer research (2003)

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... (1022 更多篇文献)

The biology and function of exosomes in cancer. ​

文献信息 ​

一句话小结 ​

在麦伴科研 (maltsci.com) 搜索更多文献 ​

摘要 ​

英文摘要 ​

麦伴智能科研服务 ​

主要研究问题 ​

核心洞察 ​

研究背景和目的 ​

主要方法/材料/实验设计 ​

关键结果和发现 ​

主要结论/意义/创新性 ​

研究局限性和未来方向 ​

参考文献 ​

引用本文的文献 ​