Fujita Yu, Yoshioka Yusuke, Ochiya Takahiro
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
Cancer Sci. 2016 Apr;107(4):385-90. doi: 10.1111/cas.12896. Epub 2016 Mar 18.
Extracellular vesicles (EV), known as exosomes and microvesicles, serve as versatile intercellular communication vehicles. Increasing evidence has shown that cancer cell-derived EV carry pathogenic components, such as proteins, messenger RNA (mRNA), microRNA (miRNA), DNA, lipids and transcriptional factors, that can mediate paracrine signaling in the tumor microenvironment. These data suggest that EV transfer of cancer pathogenic components enable long-distance crosstalk between cancer cells and distant organs, resulting in the promotion of the initial steps for pre-metastatic niche formation. Understanding the metastatic mechanisms through EV transfer may open up a new avenue for cancer therapeutic strategies. Furthermore, the circulating EV have also been of interest as a source for liquid biopsies. EV in body fluids provide a reliable source of miRNA and proteins for cancer biomarkers. The tumor-specific components in EV effectively provide various messages on the physiological and pathological status of cancer patients. Although many researchers are searching for EV biomarkers using miRNA microarrays and proteome analyses, the detection technology for circulating EV in body fluids has not yet reached the point of clinical application. In this review, we summarize recent findings regarding EV function, specifically in metastasis through the transfer of cancer pathogenic components. Furthermore, we highlight the potential of using circulating EV for cancer diagnosis.
细胞外囊泡(EV),即外泌体和微囊泡,是多功能的细胞间通讯载体。越来越多的证据表明,癌细胞衍生的EV携带致病成分,如蛋白质、信使核糖核酸(mRNA)、微小核糖核酸(miRNA)、DNA、脂质和转录因子,这些成分可在肿瘤微环境中介导旁分泌信号传导。这些数据表明,癌症致病成分的EV转移能够使癌细胞与远处器官进行远距离串扰,从而促进转移前生态位形成的初始步骤。通过EV转移了解转移机制可能为癌症治疗策略开辟一条新途径。此外,循环EV作为液体活检的来源也备受关注。体液中的EV为癌症生物标志物提供了可靠的miRNA和蛋白质来源。EV中的肿瘤特异性成分有效地提供了有关癌症患者生理和病理状态的各种信息。尽管许多研究人员正在使用miRNA微阵列和蛋白质组分析来寻找EV生物标志物,但体液中循环EV的检测技术尚未达到临床应用阶段。在本综述中,我们总结了关于EV功能的最新发现,特别是通过癌症致病成分转移在转移中的作用。此外,我们强调了使用循环EV进行癌症诊断的潜力。