过表达黑色素瘤来源的细胞外囊泡的抗转移功能。

Anti-Metastatic Function of Extracellular Vesicles Derived from -Overexpressing Melanoma.

机构信息

Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16, Naka-cho, Koganei, Tokyo 184-8588, Japan.

Department of Industrial Technology and Innovation, Tokyo University of Agriculture and Technology, 2-24-16, Naka-cho, Koganei, Tokyo 184-8588, Japan.

出版信息

Curr Oncol. 2022 Feb 11;29(2):1029-1046. doi: 10.3390/curroncol29020088.

DOI:10.3390/curroncol29020088

PMID:35200587

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8870779/

Abstract

A metastatic melanoma cell line B16-F10 (F10) was modified to a more undifferentiated state by overexpression. The produced cell line F10 showed a higher metastatic potential than F10. Instead of whole cells, the extracellular vesicles (EVs) therefrom were investigated about their possible role as an autovaccine against metastasis. EVs from F10 cells (F10-EVs) could suppress the metastasis, contrasting the EVs from less metastatic F10 cells (F10-EVs) enhanced metastasis. The involvement of TGF-β1 in the role of F10-EVs was analyzed, as TGF-β1 was a secretory cytokine being affected most intensively by overexpression. It was suggested to be crucial that the TGF-β1 concentration in F10-EVs should be as low as 1.6 pg/μg for its metastasis-suppressive role. In response to F10-EVs, immunoreaction was observed in liver, indicating the specific decrease in the number of tumor-promotive CD163-positive macrophages. These indicate a possibility of F10-EVs as a novel autovaccine candidate against melanoma metastasis.

摘要

一个转移性黑色素瘤细胞系 B16-F10（F10）通过过度表达被修饰成更未分化的状态。产生的细胞系 F10 显示出比 F10 更高的转移潜力。研究了来自该细胞系的细胞外囊泡（EVs），以探讨其作为针对转移的自体疫苗的可能作用。来自 F10 细胞的 EVs（F10-EVs）可以抑制转移，而来自转移能力较低的 F10 细胞的 EVs（F10-EVs）增强了转移。分析了 TGF-β1 在 F10-EVs 作用中的参与，因为 TGF-β1 是一种分泌细胞因子，受过度表达的影响最强烈。建议 F10-EVs 中的 TGF-β1 浓度应低至 1.6 pg/μg，以发挥其抑制转移的作用。对 F10-EVs 的反应在肝脏中观察到免疫反应，表明促进肿瘤的 CD163 阳性巨噬细胞数量特异性减少。这些表明 F10-EVs 作为一种新型针对黑色素瘤转移的自体疫苗候选物具有可能性。