Exosomes from drug-resistant breast cancer cells transmit chemoresistance by a horizontal transfer of microRNAs.
Exosomes from drug-resistant breast cancer cells transmit chemoresistance by a horizontal transfer of microRNAs.
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来自耐药乳腺癌细胞的外泌体通过 MicroRNA 的水平转移传递化疗耐药性
DOI：
10.1371/journal.pone.0095240
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tang JH
中科院分区：
文献类型：
--
作者：
Chen WX;Liu XM;Lv MM;Chen L;Zhao JH;Zhong SL;Ji MH;Hu Q;Luo Z;Wu JZ;Tang JH
阿霉素和多西紫杉醇是治疗乳腺癌的两种常用药物，但它们的疗效往往因出现化疗耐药而受到限制。最近的研究表明，外切体作为不同种类的肿瘤细胞之间交换遗传货物的载体，产生了癌症发生和发展的传递耐药。然而，乳腺癌外切体的具体作用还知之甚少。在此，我们加强了其他人的报道，即人乳腺癌细胞株MCF-7/S可以通过其耐药变异体MCF-7/Adr和MCF-7/Doc获得更高的生存潜力。此外，后者的外切体A/exo和D/exo显著调节了S/exo的细胞周期分布和药物诱导的细胞凋亡。经核糖核酸酶处理后的外切体不能调节细胞周期和细胞对凋亡的抗性，提示这是一种RNA依赖的方式。A/exo、D/exo和S/exo的miRNA表达谱芯片和聚合酶链式反应表明，它们装载了选择性的miRNA模式。在A/exo和D/exo转移到受体MCF-7/S后，获得细胞中相同的miRNAs显著增加。靶基因预测和通路分析表明，miR-100、miR-222和miR-30a参与了肿瘤发生、膜泡形成和治疗失败的通路。此外，D/exo共培养实验和miRNA模拟转染实验表明，富含miR-222的D/exo可以改变MCF-7/S中靶基因的表达。我们的结果表明，耐药乳腺癌细胞可能通过释放外切体来传播对敏感细胞的耐药性，这种作用可能部分归因于特定miRNAs的细胞间转移。
Adriamycin and docetaxel are two agents commonly used in treatment of breast cancer, but their efficacy is often limited by the emergence of chemoresistance. Recent studies indicate that exosomes act as vehicles for exchange of genetic cargo between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development and progression. However, the specific contribution of breast cancer-derived exosomes is poorly understood. Here we reinforced other's report that human breast cancer cell line MCF-7/S could acquire increased survival potential from its resistant variants MCF-7/Adr and MCF-7/Doc. Additionally, exosomes of the latter, A/exo and D/exo, significantly modulated the cell cycle distribution and drug-induced apoptosis with respect to S/exo. Exosomes pre-treated with RNase were unable to regulate cell cycle and apoptosis resistance, suggesting an RNA-dependent manner. Microarray and polymerase chain reaction for the miRNA expression profiles of A/exo, D/exo, and S/exo demonstrated that they loaded selective miRNA patterns. Following A/exo and D/exo transfer to recipient MCF-7/S, the same miRNAs were significantly increased in acquired cells. Target gene prediction and pathway analysis showed the involvement of miR-100, miR-222, and miR-30a in pathways implicated in cancer pathogenesis, membrane vesiculation and therapy failure. Furthermore, D/exo co-culture assays and miRNA mimics transfection experiments indicated that miR-222-rich D/exo could alter target gene expression in MCF-7/S. Our results suggest that drug-resistant breast cancer cells may spread resistance capacity to sensitive ones by releasing exosomes and that such effects could be partly attributed to the intercellular transfer of specific miRNAs.
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影响因子：
5.2
作者：
Fonsato, Valentina;Collino, Federica;Herrera, Maria Beatriz;Cavallari, Claudia;Deregibus, Maria Chiara;Cisterna, Barbara;Bruno, Stefania;Romagnoli, Renato;Salizzoni, Mauro;Tetta, Ciro;Camussi, Giovanni
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4.2
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影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.
影响因子：
3.7
作者：
Corcoran C;Rani S;O'Brien K;O'Neill A;Prencipe M;Sheikh R;Webb G;McDermott R;Watson W;Crown J;O'Driscoll L
通讯作者：
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