Tumour Cells Incorporate Exosomes Derived from Dendritic Cells through a Mechanism Involving the Tetraspanin CD9

Q3 Medicine

Journal of Circulating Biomarkers Pub Date : 2013-01-01 DOI:10.5772/52069

G. Romagnoli, P. A. Toniolo, Isabela Katz Migliori, E. Caldini, M. A. Ferreira, C. R. Pizzo, P. C. Bergami-Santos, J. Barbuto

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引用次数: 7

Abstract

Exosomes (Exos) are secreted nanovesicles that contain membrane proteins and genetic material, which can be transferred between cells and contribute to their communication in the body. We show that Exos, obtained from mature human dendritic cells (DCs), are incorporated by tumour cells, which after Exos treatment, acquire the expression of HLA-class I, HLA-class II, CD86, CD11c, CD54 and CD18. This incorporation reaches its peak eight hours after treatment, can be observed in different cell tumour lines (SK-BR-3, U87 and K562) and could be a means to transform non-immunogenic into immunogenic tumour cells. Interestingly, tetraspanins, which are expressed by the tumour cells, have their surface level decreased after Exo treatment. Furthermore, the intensity of Exo incorporation by the different tumour cell lines was proportional to their CD9 expression levels and pre-treatment of Exos with anti-CD9 decreased their incorporation (by SK-BR-3 cells). This modification of tumour cells by DC-derived Exos may allow their use in new immunotherapeutic approaches to cancer. Furthermore, by showing the involvement of CD9 in this incorporation, we provide a possible selection criterion for tumours to be addressed by this strategy.

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肿瘤细胞通过与四蛋白CD9相关的机制整合来自树突状细胞的外泌体

外泌体(Exos)是分泌的纳米囊泡，含有膜蛋白和遗传物质，可以在细胞之间转移，并有助于它们在体内的交流。我们发现，从成熟的人树突状细胞(dc)中获得的Exos与肿瘤细胞结合，经过Exos处理后，肿瘤细胞获得hla - I类、hla - II类、CD86、CD11c、CD54和CD18的表达。这种结合在治疗后8小时达到峰值，可以在不同的细胞肿瘤系(SK-BR-3、U87和K562)中观察到，可能是将非免疫原性肿瘤细胞转化为免疫原性肿瘤细胞的一种手段。有趣的是，肿瘤细胞表达的四联蛋白在Exo治疗后其表面水平降低。此外，不同肿瘤细胞系的Exo掺入强度与其CD9表达水平成正比，用抗CD9预处理Exo可以减少它们的掺入(SK-BR-3细胞)。这种由dc衍生的Exos修饰的肿瘤细胞可能允许它们在新的癌症免疫治疗方法中使用。此外，通过显示CD9参与这种结合，我们提供了一种可能的肿瘤选择标准，通过这种策略来解决。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Circulating Biomarkers Medicine-Biochemistry (medical)

CiteScore

3.20

自引率

0.00%

发文量

审稿时长

8 weeks

期刊介绍： Journal of Circulating Biomarkers is an international, peer-reviewed, open access scientific journal focusing on all aspects of the rapidly growing field of circulating blood-based biomarkers and diagnostics using circulating protein and lipid markers, circulating tumor cells (CTC), circulating cell-free DNA (cfDNA) and extracellular vesicles, including exosomes, microvesicles, microparticles, ectosomes and apoptotic bodies. The journal publishes high-impact articles that deal with all fields related to circulating biomarkers and diagnostics, ranging from basic science to translational and clinical applications. Papers from a wide variety of disciplines are welcome; interdisciplinary studies are especially suitable for this journal. Included within the scope are a broad array of specialties including (but not limited to) cancer, immunology, neurology, metabolic diseases, cardiovascular medicine, regenerative medicine, nosology, physiology, pathology, technological applications in diagnostics, therapeutics, vaccine, drug delivery, regenerative medicine, drug development and clinical trials. The journal also hosts reviews, perspectives and news on specific topics.