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肿瘤细胞衍生的外泌体在多器官肿瘤发生过程中信使核糖核酸的细胞间转移

Intercellular transfer of messenger RNAs in multiorgan tumorigenesis by tumor cell-derived exosomes.

作者信息

Jiang Hong, Li Zheng, Li Xiaohua, Xia Jianguo

机构信息

Department of Gastrointestinal Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.

Department of Food Science and Human Nutrition, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611, USA.

出版信息

Mol Med Rep. 2015 Jun;11(6):4657-63. doi: 10.3892/mmr.2015.3312. Epub 2015 Feb 6.

DOI:10.3892/mmr.2015.3312
PMID:25673258
Abstract

Exosomes are small membrane vesicles of endocytic origin. They are derived from various cells, including tumor cells, and may serve as important modulators of intercellular communication. The present study established a U‑87 MG human glioblastoma cell line that showed a stable expression of green fluorescent protein (GFP; U‑87‑GFP). Two types of human tumor cell lines, U‑87‑GFP and LoVo human colon cancer cells, were demonstrated to communicate through the transfer of GFP messenger (m)RNA by exosomes. Furthermore, GFP mRNAs delivered by the U‑87‑GFP cell‑derived exosomes were translated into functional proteins in the recipient LoVo cells. In addition, LoVo cells were demonstrated to uptake exosomes derived from the U‑87‑GFP cells by clathrin‑mediated endocytosis. These results indicate that tumor cell‑derived exosomes may represent vesicular carriers that regulate gene expression, which may provide a pathway of intercellular communication in the tumor microenvironment during multiorgan tumorigenesis. The exosome uptake pathway may have potential therapeutic applications in multiorgan tumorigenesis.

摘要

外泌体是内吞起源的小膜泡。它们来源于包括肿瘤细胞在内的各种细胞,并且可能作为细胞间通讯的重要调节因子。本研究建立了一种稳定表达绿色荧光蛋白(GFP;U-87-GFP)的U-87 MG人胶质母细胞瘤细胞系。两种人类肿瘤细胞系,U-87-GFP和LoVo人结肠癌细胞,被证明可通过外泌体转移GFP信使核糖核酸(mRNA)进行通讯。此外,由U-87-GFP细胞衍生的外泌体递送的GFP mRNA在受体LoVo细胞中被翻译成功能性蛋白质。另外,LoVo细胞被证明通过网格蛋白介导的内吞作用摄取源自U-87-GFP细胞的外泌体。这些结果表明,肿瘤细胞衍生的外泌体可能代表调节基因表达的囊泡载体,这可能在多器官肿瘤发生过程中为肿瘤微环境中的细胞间通讯提供一条途径。外泌体摄取途径可能在多器官肿瘤发生中具有潜在的治疗应用。

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