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头颈部癌细胞来源的细胞外囊泡 cargo 可破坏树突状细胞功能并与血浆 microRNAs 相匹配。

Extracellular vesicles cargo from head and neck cancer cell lines disrupt dendritic cells function and match plasma microRNAs.

机构信息

Centro de Pesquisa Experimental, Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Sao Paulo, Brazil.

Head and Neck Surgery Department, Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil.

出版信息

Sci Rep. 2021 Sep 17;11(1):18534. doi: 10.1038/s41598-021-97753-y.

Abstract

Extracellular vesicles (EVs) are mediators of the immune system response. Encapsulated in EVs, microRNAs can be transferred between cancer and immune cells. To define the potential effects of EVs originated from squamous cell carcinoma cells on immune system response, we performed microRNA profiling of EVs released from two distinct cell lines and treated dendritic cells derived from circulating monocytes (mono-DCs) with these EVs. We confirmed the internalization of EVs by mono-DCs and the down-regulation of microRNA mRNA targets in treated mono-DCs. Differences in surface markers of dendritic cells cultivated in the presence of EVs indicated that their content disrupts the maturation process. Additionally, microRNAs known to interfere with dendritic cell function, and detected in EVs, matched microRNAs from squamous cell carcinoma patients' plasma: miR-17-5p in oropharyngeal squamous cell carcinoma, miR-21 in oral squamous cell carcinoma, miR-16, miR-24, and miR-181a circulating in both oral and oropharyngeal squamous cell carcinoma, and miR-23b, which has not been previously described in plasma of head and neck squamous cell carcinoma, was found in plasma from patients with these cancer subtypes. This study contributes with insights on EVs in signaling between cancer and immune cells in squamous cell carcinoma of the head and neck.

摘要

细胞外囊泡 (EVs) 是免疫系统反应的介质。微小 RNA (miRNAs) 包裹在 EVs 中,可以在癌细胞和免疫细胞之间转移。为了定义源自鳞状细胞癌细胞的 EVs 对免疫系统反应的潜在影响,我们对来自两种不同细胞系的 EVs 进行了 miRNA 谱分析,并将这些 EVs 用于处理源自循环单核细胞的树突状细胞 (mono-DCs)。我们证实了 mono-DCs 对 EVs 的内化以及处理后的 mono-DCs 中 miRNA mRNA 靶标的下调。在 EVs 存在下培养的树突状细胞表面标志物的差异表明其内容物破坏了成熟过程。此外,在 EVs 中检测到已知干扰树突状细胞功能的 microRNAs,与鳞状细胞癌患者血浆中的 microRNAs 相匹配:口咽鳞状细胞癌中的 miR-17-5p、口腔鳞状细胞癌中的 miR-21、口腔和口咽鳞状细胞癌中循环的 miR-16、miR-24 和 miR-181a,以及之前未在头颈部鳞状细胞癌的血浆中描述过的 miR-23b,在这些癌症亚型患者的血浆中被发现。本研究有助于了解头颈部鳞状细胞癌中癌症与免疫细胞之间 EVs 的信号转导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/621c/8448882/3c433df9fef0/41598_2021_97753_Fig1_HTML.jpg

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