Human tumor virus utilizes exosomes for intercellular communication
Human tumor virus utilizes exosomes for intercellular communication
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DOI：
10.1073/pnas.1014194107
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发表时间：
2010-11-23
影响因子：
11.1
通讯作者：
Raab-Traub, Nancy
中科院分区：
文献类型：
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作者：
Meckes, David G., Jr.;Shair, Kathy H. Y.;Raab-Traub, Nancy
EB病毒潜伏膜蛋白1(LMP1)在多种人类恶性肿瘤中均有表达，对细胞生长有重要影响。它已在外切体中被检测到，并显示出抑制免疫功能。Exosome是含有蛋白质、mRNAs和microRNAs(MiRNAs)的小的分泌细胞囊泡。当它们由恶性细胞产生时，可以促进血管生成、细胞增殖、肿瘤细胞侵袭和免疫逃避。在这项研究中，从携带潜伏EBV的鼻咽癌(NPC)细胞释放的外体含有LMP1、信号转导分子和病毒编码的miRNAs。暴露于这些NPC外切体会激活受体细胞中的ERK和AKT信号通路。有趣的是，鼻咽癌外体也含有病毒miRNAs，其中几个与其细胞内水平相比有所丰富。LMP1在EBV阴性的上皮细胞系中诱导EGF受体的表达，由这些细胞产生的外体也在外体中含有高水平的EGF受体。这些发现表明，EBV和LMP1对细胞表达的影响也调节外切体的内容和性质。外体可能通过LMP1、信号分子和病毒miRNAs的细胞间转移来操纵肿瘤微环境来影响邻近细胞的生长。
The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is expressed in multiple human malignancies and has potent effects on cell growth. It has been detected in exosomes and shown to inhibit immune function. Exosomes are small secreted cellular vesicles that contain proteins, mRNAs, and microRNAs (miRNAs). When produced by malignant cells, they can promote angiogenesis, cell proliferation, tumor-cell invasion, and immune evasion. In this study, exosomes released from nasopharyngeal carcinoma (NPC) cells harboring latent EBV were shown to contain LMP1, signal transduction molecules, and virus-encoded miRNAs. Exposure to these NPC exosomes activated the ERK and AKT signaling pathways in the recipient cells. Interestingly, NPC exosomes also contained viral miRNAs, several of which were enriched in comparison with their intracellular levels. LMP1 induces expression of the EGF receptor in an EBV-negative epithelial cell line, and exosomes produced by these cells also contain high levels of EGF receptor in exosomes. These findings suggest that the effects of EBV and LMP1 on cellular expression also modulate exosome content and properties. The exosomes may manipulate the tumor microenvironment to influence the growth of neighboring cells through the intercellular transfer of LMP1, signaling molecules, and viral miRNAs.