A Comprehensive Proteomics Analysis Reveals a Secretory Path- and Status-Dependent Signature of Exosomes Released from Tumor-Associated Macrophages

详细信息    查看全文

• 作者：Yinghui Zhu ; Xianwei Chen ; Qingfei Pan ; Yang Wang ; Siyuan Su ; Cuicui Jiang ; Yang Li ; Ningzhi Xu ; Lin Wu ; Xiaomin Lou ; Siqi Liu
• 刊名：Journal of Proteome Research
• 出版年：2015
• 出版时间：October 2, 2015
• 年：2015
• 卷：14
• 期：10
• 页码：4319-4331
• 全文大小：482K
• ISSN：1535-3907

文摘

Exosomes are 30鈥?20 nm-sized membrane vesicles of endocytic origin that are released into the extracellular environment and play roles in cell鈥揷ell communication. Tumor-associated macrophages (TAMs) are important constituents of the tumor microenvironment; thus, it is critical to study the features and complex biological functions of TAM-derived exosomes. Here, we constructed a TAM cell model from a mouse macrophage cell line, Ana-1, and performed comparative proteomics on exosomes, exosome-free media, and cells between TAMs and Ana-1. Proteomic analysis between exosome and exosome-free fractions indicated that the functions of exosome dominant proteins were mainly enriched in RNA processing and proteolysis. TAM status dramatically affected the abundances of 20S proteasome subunits and ribosomal proteins in their exosomes. The 20S proteasome activity assay strongly indicated that TAM exosomes possessed higher proteolytic activity. In addition, Ana-1- and TAM-derived exosomes have different RNA profiles, which may result from differential RNA processing proteins. Taken together, our comprehensive proteomics study provides novel views for understanding the complicated roles of macrophage-derived exosomes in the tumor microenvironment.