Comparative Study of Metastasis Suppression Effects of Extracellular Vesicles Derived from Anaplastic Cell Lines, Nanog-Overexpressing Melanoma, and Induced Pluripotent Stem Cells

被引:2
|
作者
Khoo, Celine Swee May [1 ]
Henmi, Takuya [1 ]
Saito, Mikako [1 ,2 ]
机构
[1] Tokyo Univ Agr & Technol, Dept Biotechnol & Life Sci, 2-24-16 Naka Cho, Koganei, Tokyo 1848588, Japan
[2] Tokyo Univ Agr & Technol, Bioresource Labs, 2-24-16 Naka Cho, Koganei, Tokyo 1848588, Japan
关键词
melanoma B16-F10; Nanog; iPS cells; anaplastic cells; metastasis;
D O I
10.3390/ijms242417206
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous studies have demonstrated that extracellular vesicles (EVs) derived from an anaplastic mouse melanoma cell line made using Nanog overexpression of F10 (Nanog+F10) suppressed the metastasis of Nanog+F10. Here, an induced pluripotent stem (iPS) cell line was focused as a more anaplastic cell line, potentially producing EVs with higher metastasis-suppressive effects. The EVs were introduced into the tail vein nine times before introducing Nanog+F10 cells. Two weeks later, the liver and lung were resected and metastatic colonies were quantified. The involvement of macrophages (invasion inhibiting ability, phagocytic activity) and cytotoxic T cells (cytotoxicity) was evaluated using J774.1 and CTLL-2 cell lines. iPS EVs showed similar level effects to Nanog+F10 EVs in every item relevant to metastasis suppression. Differential expression analysis of miRNAs in EVs and functional network database analysis revealed that dominant regulatory miRNAs were predicted. The candidate hub genes most highly associated with the metastasis suppression mechanism were predicted as six genes, including Trp53 and Hif1a, for Nanog+F10 EVs and ten genes, including Ins1 and Kitl, for iPS EVs. Regarding the mechanism, Nanog+F10 EVs and iPS EVs were very different. This suggests synergistic effect when used together as metastasis preventive vaccine.
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页数:22
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