Extracellular vesicles carry microRNA-195 to intrahepatic cholangiocarcinoma and improve survival in a rat model.
Extracellular vesicles carry microRNA-195 to intrahepatic cholangiocarcinoma and improve survival in a rat model.
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细胞外囊泡将microRNA-195携带到肝内胆管癌并改善大鼠模型中的存活率。
DOI：
10.1002/hep.28735
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Selaru FM
中科院分区：
文献类型：
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作者：
Li L;Piontek K;Ishida M;Fausther M;Dranoff JA;Fu R;Mezey E;Gould SJ;Fordjour FK;Meltzer SJ;Sirica AE;Selaru FM
癌症微环境在癌症的发生、生长和体内平衡中发挥着核心作用。这种范式表明，癌症成纤维细胞支持癌症，可能是对从癌细胞接收到的刺激做出的反应。我们的目的是研究细胞外囊泡 (EV) 是否可以在癌症相关成纤维细胞和癌细胞之间转运 microRNA (miR)。为此，我们根据已发布的协议提取了 EV。通过 qRT-PCR 研究 EV 的 miR 含量。 EVs 用选定的 miR 物种转染，并在体外和体内用于胆管癌大鼠模型。我们发现 miR-195 在胆管癌细胞以及邻近的成纤维细胞中下调。此外，我们报告 EV 将 miR-195 从成纤维细胞运送到癌细胞。最后，我们表明，载有 miR-195 的成纤维细胞来源的 EV 可以在胆管癌大鼠模型中给药，集中在肿瘤内，减小癌症的大小，并提高治疗大鼠的生存率。 EVs 在人类 CCA 中癌细胞和癌症相关成纤维细胞之间运输 miR 物种方面发挥着重要作用。了解这些机制可能有助于设计新的疗法。
The cancer microenvironment plays a central role in cancer development, growth and homeostasis. This paradigm suggests that cancer fibroblasts support cancers, probably in response to stimuli received from the cancer cells. We aimed at investigating if extracellular vesicles (EVs) can shuttle microRNA (miR) species between cancer associated fibroblasts and cancer cells. To this end, we extracted EVs according to published protocols. EVs were studied for their miR content by qRT-PCR. EVs were transfected with select miR species and utilized in vitro as well as in vivo in a rat model of cholangiocarcinoma. We found that miR-195 is downregulated in cholangiocarcinoma cells, as well as in adjoining fibroblasts. Furthermore, we report that EVs shuttle miR-195 from fibroblasts to cancer cells. Lastly, we show that fibroblast-derived EVs, loaded with miR-195, can be administered in a rat model of cholangiocarcinoma, concentrate within the tumor, decrease the size of cancers, and improve survival of treated rats. EVs play a salient role in trafficking miR species between cancer cells and cancer associated fibroblasts in human CCA. Understanding of these mechanisms may allow devising of novel therapeutics.