The multifaceted exosome: biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities.

The multifaceted exosome: biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities.
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DOI:
10.1016/j.bcp.2011.12.037
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发表时间:
2012-06-01
影响因子:
5.8
通讯作者:
Burczynski ME
Burczynski ME
中科院分区:
医学2区
文献类型:
--
作者:
Pant S;Hilton H;Burczynski ME

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胞外体是释放到周围生物体液中的纳米大小的细胞囊泡。它们含有亲本细胞的RNA、DNA、蛋白质和脂肪成分,反映了细胞的状况,有望成为具有精致特异性的生物标记物。外体是来自细胞内膜系统的生物活性囊泡,并分泌到周围的体液中。外切体包含细胞和细胞状态特定的蛋白质、信使核糖核酸和miRNA。考虑到外切体被认为在各种病理条件下所起的作用,外切体的形成、货物内容物和向周围细胞的传递具有巨大的生物学意义。它们帮助免疫细胞提呈抗原,并可根据亲本抗原提呈细胞的条件而表现出抗炎或促炎特性。病毒可以劫持宿主细胞的外体机器,以躲避宿主防御系统,从而帮助病毒的反式感染。肿瘤来源的外切体可能通过递送蛋白质、信使核糖核酸和miRNA来帮助系统地建立致癌生态位,这些蛋白质、信使核糖核酸和miRNA有助于血管生成、细胞增殖和细胞存活。外切体也与神经退行性疾病的传播有关。研究表明,外切体在释放后被远端的细胞选择性地摄取。由于它们的活性分子货物,它们可以对受体细胞进行重新编程。细胞谱系和特定状态的外切体意味着,它们可能因此拥有基于体液的生物标记物,具有无与伦比的准确性,特别是对于难以或不可能获得的组织。外切体特异的膜蛋白提供了识别和选择外切体的标记,而细胞类型和细胞条件特定的蛋白质、mRNA和miRNA货物提供了丰富的潜在生物标记来源。这篇综述旨在提供在新兴的外体生物学领域的科学现状的概述。
Exosomes are nanometer sized cellular vesicles released into surrounding bio-fluids. Containing the parent cell's RNA, DNA, protein and lipid component, they reflect the cell's condition and hold promise as biomarkers of exquisite specificity. Exosomes are bioactive vesicles derived from the cell's endosomal membrane system and secreted into surrounding body fluids. Exosomes contain cell and cell-state specific cargos of protein, mRNA and miRNA. Exosome formation, cargo content, and delivery to surrounding cells is of immense biological interest considering the role that exosomes are believed to play in various pathological conditions. They aid antigen presentation by immune cells and can exhibit either anti-inflammatory or pro-inflammatory properties depending on the parent antigen-presenting cell's conditioning. Viruses can hijack a host cell's exosomal machinery to evade host defense systems aiding in the trans-infection of viruses. Tumor derived exosomes may help establish an oncogenic niche systemically via delivery of protein, mRNA, and miRNA that can aid angiogenesis, cell proliferation, and cell survival. Exosomes have also been implicated in the spread of neurodegenerative diseases. Studies have shown that exosomes are selectively taken up by cells distal from their release. They can reprogram the recipient cells due to their active molecular cargo. Cell-lineage and state-specific exosomes imply that they may therefore harbor body fluid-based biomarkers of unparalleled accuracy, particularly for tissues that are difficult or impossible to access. Exosome-specific membrane proteins provide markers enabling exosome identity and selection, while cell type and cell condition-specific protein, mRNA and miRNA cargo provide a rich potential source of biomarkers. This review serves to provide an overview of the current state of the science in the burgeoning field of exosome biology.
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