The Phenotypic Effects of Exosomes Secreted from Distinct Cellular Sources: a Comparative Study Based on miRNA Composition.
The Phenotypic Effects of Exosomes Secreted from Distinct Cellular Sources: a Comparative Study Based on miRNA Composition.
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DOI：
10.1208/s12248-018-0227-4
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发表时间：
2018-04-30
期刊：
影响因子：
--
通讯作者：
Nguyen J
中科院分区：
文献类型：
--
作者：
Ferguson S;Kim S;Lee C;Deci M;Nguyen J
外切体是由脂类、蛋白质和核酸组成的纳米大小的囊泡。它们的分子图谱是多样的，来自不同细胞类型的外切体具有不同的生物学活性。由于胞外体现在被用作外源治疗货物的输送载体，因此必须了解它们的内在特性和生物学效应。我们进行了miRNA图谱分析，发现前列腺癌(PC3)和人胚胎肾(HEK)293外显子的miRNA图谱有很大差异，而常见miRNAs的丰度几乎没有相关性(R2=0.16)。利用系统水平的生物信息学方法，预测在PC3exosome而不是HEKexosome中最丰富的β显著调节整合素信号，整合素-miRNA3缺失导致巨噬细胞M2极化。PC3而不是HEK外切体下调整合素-β3的表达水平达70%。当用PC3来源的外切体而不是HEK来源的外切体处理时，RAW 264.7巨噬细胞有向M2表型转变的剂量依赖性极化。相反，被广泛用作递送载体的HEK外切体被预测为靶向钙粘素信号，实验验证表明，HEK外切体处理的MCF7乳腺癌细胞的迁移潜力显著增加。即使广泛使用的外切体也不太可能是惰性的，它们的内在活性应该在治疗部署之前进行评估。
Exosomes are nano-sized vesicles composed of lipids, proteins, and nucleic acids. Their molecular landscape is diverse, and exosomes derived from different cell types have distinct biological activities. Since exosomes are now being utilized as delivery vehicles for exogenous therapeutic cargoes, their intrinsic properties and biological effects must be understood. We performed miRNA profiling and found substantial differences in the miRNA landscape of prostate cancer (PC3) and human embryonic kidney (HEK) 293 exosomes with little correlation in abundance of common miRNAs (R2=0.16). Using a systems-level bioinformatics approach, the most abundant miRNAs in PC3 exosomes but not HEK exosomes were predicted to significantly modulate integrin signaling, with integrin-β3 loss inducing macrophage M2 polarization. PC3 but not HEK exosomes downregulated integrin-β3 expression levels by 70%. There was a dose-dependent polarization of RAW 264.7 macrophages toward an M2 phenotype when treated with PC3-derived exosomes but not HEK-derived exosomes. Conversely, HEK exosomes, widely utilized as delivery vehicles were predicted to target cadherin signaling, with experimental validation showing a significant increase in the migratory potential of MCF7 breast cancer cells treated with HEK exosomes. Even widely utilized exosomes are unlikely to be inert, and their intrinsic activity ought to be assessed before therapeutic deployment.
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影响因子：
3.7
作者：
Jablonski KA;Amici SA;Webb LM;Ruiz-Rosado Jde D;Popovich PG;Partida-Sanchez S;Guerau-de-Arellano M
通讯作者：
Guerau-de-Arellano M
影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
DOI：
10.1073/pnas.1521230113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Kowal, Joanna;Arras, Guillaume;Thery, Clotilde
通讯作者：
Thery, Clotilde
N-钙粘着蛋白在乳腺癌细胞中的外源表达会诱导细胞迁移，侵袭和转移。
影响因子：
7.8
作者：
Hazan, R B;Phillips, G R;Qiao, R F;Norton, L;Aaronson, S A
通讯作者：
Aaronson, S A
DOI：
10.4049/jimmunol.1202496
发表时间：
2013-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Banerjee S;Xie N;Cui H;Tan Z;Yang S;Icyuz M;Abraham E;Liu G
通讯作者：
Liu G