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白血病衍生的外泌体可诱导非肿瘤星形胶质细胞发生与肿瘤发生相关的反应。

Leukemia-derived Exosomes Can Induce Responses Related to Tumorigenesis on Non-tumoral Astrocytes.

机构信息

Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.

Research Center for Animal Development Applied Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.

出版信息

Appl Biochem Biotechnol. 2023 Dec;195(12):7624-7637. doi: 10.1007/s12010-023-04428-7. Epub 2023 Apr 17.

Abstract

Cancer is the second cause of disability and death worldwide. Identifying communication between cancer cells and normal cells can shed light on the underlying metastatic mechanisms. Among different suspected mechanisms, exosomes derived from cancer cells have been introduced as a main key player in metastatic processes. To this point, we evaluated the effects of exosomes derived from the leukemia nalm6 cell line on astrocytes behavior, such as proliferation and inflammatory pathways. To assess astrocyte responses, data were obtained by MTT, Annexin/PI to indicate proliferation and apoptosis. Further analyses were performed by Real-time PCR and western blot to assess the expression of IL6, IL1β, NFkβ, TNFα, and aquaporin-4 (AQP4). Our results demonstrated that the proliferation of astrocytes was significantly increased when treated with exosomes derived from Nalm6 cells. We also found that the expression of IL6, IL1β, NFkβ, and TNFα were significantly increased at the mRNA level when exposed to exosomes derived from Nalm6 cells. Finally, the mRNA and protein levels of AQP4 were profoundly increased after being treated by exosomes derived from Nalm6 cells. To sum up, our data indicated that the secretion of cancer cells could induce responses related to tumorigenesis. However, further studies on this topic are warranted to clarify exosomes' role in metastasis.

摘要

癌症是全球范围内导致残疾和死亡的第二大原因。鉴定癌细胞与正常细胞之间的通讯可以揭示潜在的转移机制。在不同的可疑机制中,源自癌细胞的外泌体已被认为是转移过程中的主要关键因素。在这一点上,我们评估了白血病 nalm6 细胞系来源的外泌体对星形胶质细胞行为的影响,例如增殖和炎症途径。为了评估星形胶质细胞的反应,通过 MTT、Annexin/PI 来指示增殖和凋亡来获得数据。通过 Real-time PCR 和 Western blot 进一步分析来评估 IL6、IL1β、NFkβ、TNFα 和水通道蛋白-4 (AQP4) 的表达。我们的结果表明,当用源自 Nalm6 细胞的外泌体处理时,星形胶质细胞的增殖显著增加。我们还发现,当暴露于源自 Nalm6 细胞的外泌体时,IL6、IL1β、NFkβ 和 TNFα 的表达在 mRNA 水平上显著增加。最后,在用源自 Nalm6 细胞的外泌体处理后,AQP4 的 mRNA 和蛋白水平均显著增加。总之,我们的数据表明癌细胞的分泌可以诱导与肿瘤发生相关的反应。然而,需要进一步研究这个课题,以阐明外泌体在转移中的作用。

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