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自然杀伤细胞对肿瘤细胞衍生外泌体的摄取特性分析

Uptake Characterization of Tumor Cell-derived Exosomes by Natural Killer Cells.

作者信息

Huyan Ting, DU Yongyong, Huang Qiuping, Huang Qingsheng, Li Qi

机构信息

Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Youyi Xilu, Xi'an 710072, Shaanxi, P. R. China.

出版信息

Iran J Public Health. 2018 Jun;47(6):803-813.

Abstract

BACKGROUND

Cancer is the leading cause of death in human disease and is a major public health problem around the world. Exosomes are a promising cancer biomarker and therapy target. Recent evidence demonstrate that tumor cells could inhibit natural killer (NK) cells' immune surveillance function by releasing exosomes into tumor microenvironment. The intercelluar uptake of tumor cell-derived exosomes by NK cells is vital for using these exosomes in tumor diagnose and therapy. We aimed to investigate the efficiency of NK cell uptake of tumor exosomes.

METHODS

Exosomes derived from different tumor cells, RAW264.7 cells and NK cells were labeled by fluorescent dye and co-cultured with NK cells. The uptake rates of NK cells were observed by fluorescence microscope and analyzed by flow cytometry.

RESULTS

NK cells could take up more exosomes from themselves and cell lines originating from bone marrow. Epithelial cell lines can take up more exosomes from epithelial cells. There was no significant difference in uptake efficiency between Jurkat cells and RAW264.7 cells by NK cells, indicating that maybe the origin other than species affects the efficiency of recipient cell uptake of exosomes. Different tumor cells derived exosomes had different uptake efficiency by NK cells.

CONCLUSION

There is certain pattern of NK cells uptake tumor exosomes, which provide important insights on how tumors affect NK cells and develop appropriate countermeasures. In addition, it can be also helpful to select and design proper exosomes as a drug carrier in future.

摘要

背景

癌症是人类疾病中的主要死因,是全球重大的公共卫生问题。外泌体是一种很有前景的癌症生物标志物和治疗靶点。最近的证据表明,肿瘤细胞可通过向肿瘤微环境中释放外泌体来抑制自然杀伤(NK)细胞的免疫监视功能。NK细胞对肿瘤细胞来源外泌体的细胞间摄取对于在肿瘤诊断和治疗中利用这些外泌体至关重要。我们旨在研究NK细胞摄取肿瘤外泌体的效率。

方法

用荧光染料标记来自不同肿瘤细胞、RAW264.7细胞和NK细胞的外泌体,并与NK细胞共培养。通过荧光显微镜观察NK细胞的摄取率,并通过流式细胞术进行分析。

结果

NK细胞能摄取更多自身及源自骨髓的细胞系所产生的外泌体。上皮细胞系能摄取更多上皮细胞来源的外泌体。NK细胞对Jurkat细胞和RAW264.7细胞的摄取效率无显著差异,这表明可能除物种外的其他来源会影响受体细胞对外泌体的摄取效率。不同肿瘤细胞来源的外泌体被NK细胞摄取的效率不同。

结论

NK细胞摄取肿瘤外泌体存在一定规律,这为了解肿瘤如何影响NK细胞以及制定合适的应对措施提供了重要见解。此外,这对未来选择和设计合适的外泌体作为药物载体也可能有帮助。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e542/6077638/7284d7a98e42/IJPH-47-803-g001.jpg

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