微泡
外体
肿瘤微环境
免疫系统
生物
癌症研究
促炎细胞因子
细胞因子
细胞生物学
免疫学
炎症
小RNA
生物化学
基因
作者
Luize Gonçalves Lima,Sunyoung Ham,Hyunku Shin,Edna Pei Zhi Chai,Erica S. H. Lek,Richard J. Lobb,Alexandra Müller,Suresh Mathivanan,Belinda Yeo,Yeonho Choi,Belinda S. Parker,Andreas Möller
标识
DOI:10.1038/s41467-021-23946-8
摘要
Abstract Metastatic spread of a cancer to secondary sites is a coordinated, non-random process. Cancer cell-secreted vesicles, especially exosomes, have recently been implicated in the guidance of metastatic dissemination, with specific surface composition determining some aspects of organ-specific localization. Nevertheless, whether the tumor microenvironment influences exosome biodistribution has yet to be investigated. Here, we show that microenvironmental cytokines, particularly CCL2, decorate cancer exosomes via binding to surface glycosaminoglycan side chains of proteoglycans, causing exosome accumulation in specific cell subsets and organs. Exosome retention results in changes in the immune landscape within these organs, coupled with a higher metastatic burden. Strikingly, CCL2-decorated exosomes are directed to a subset of cells that express the CCL2 receptor CCR2, demonstrating that exosome-bound cytokines are a crucial determinant of exosome-cell interactions. In addition to the finding that cytokine-conjugated exosomes are detected in the blood of cancer patients, we discovered that healthy subjects derived exosomes are also associated with cytokines. Although displaying a different profile from exosomes isolated from cancer patients, it further indicates that specific combinations of cytokines bound to exosomes could likewise affect other physiological and disease settings.
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