Exosomal transfer of functional small RNAs mediates cancer-stroma communication in human endometrium.
Exosomal transfer of functional small RNAs mediates cancer-stroma communication in human endometrium.
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作者：
Maida Y;Takakura M;Nishiuchi T;Yoshimoto T;Kyo S
外体是由多种类型的细胞分泌的小的膜泡。最近的证据表明，人类细胞之间通过交换外切体进行交流。癌细胞与邻近的间质细胞密切相互作用，并通过双向交流共同促进疾病。在这里，我们研究了外切体是否可以在癌细胞和邻近的成纤维细胞之间的细胞间通讯中发挥作用。从正常子宫内膜组织和子宫内膜癌组织中分离子宫内膜成纤维细胞，并检测子宫内膜癌细胞系石川氏来源的外切体的细胞间转移。分离的成纤维细胞在表达CD63-GFP的Ishikawa细胞的条件培养液中培养，我们发现GFP阳性的外切体从Ishikawa细胞转移到成纤维细胞。接下来，我们将荧光素酶基因的shRNA导入石川细胞。该shRNA被包裹在外切体中，并被转移到成纤维细胞中，然后下调成纤维细胞中荧光素酶的表达。石川衍生的外切体中自然表达的成熟microRNAs也被转运到子宫内膜成纤维细胞中，它们改变了成纤维细胞的microRNA表达谱。这些结果表明，子宫内膜癌细胞可以通过外切体将小的调控RNA传递给子宫内膜成纤维细胞。我们的发现证明了一种以前未知的人类子宫内膜癌细胞和相关成纤维细胞之间的细胞间通讯模式。
Exosomes are small membrane vesicles secreted from a variety of cell types. Recent evidence indicates that human cells communicate with each other by exchanging exosomes. Cancer cells closely interact with neighboring stromal cells, and together they cooperatively promote disease via bidirectional communication. Here, we investigated whether exosomes can play roles in intercellular communication between cancer cells and neighboring fibroblasts. Endometrial fibroblasts were isolated from normal endometrial tissues and from endometrial cancer tissues, and cell‐to‐cell transfer of endometrial cancer cell line Ishikawa‐derived exosomes was examined. The isolated fibroblasts were cultured in conditioned media from CD63‐GFP‐expressing Ishikawa cells, and we found that GFP‐positive exosomes were transferred from Ishikawa cells to the fibroblasts. Next, we introduced a shRNA for a luciferase gene into Ishikawa cells. This shRNA was encapsulated into exosomes, was transferred to the fibroblasts, and then downregulated luciferase expression in the fibroblasts. The mature microRNAs naturally expressed in Ishikawa‐derived exosomes were also transported into the endometrial fibroblasts, and they altered the microRNA expression profiles of the fibroblasts. These results indicated that endometrial cancer cells could transmit small regulatory RNAs to endometrial fibroblasts via exosomes. Our findings document a previously unknown mode of intercellular communication between cancer cells and related fibroblasts in human endometrium.