RNA Trafficking by Acute Myelogenous Leukemia Exosomes
RNA Trafficking by Acute Myelogenous Leukemia Exosomes
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DOI：
10.1158/0008-5472.can-12-2184
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发表时间：
2013-01-15
期刊：
影响因子：
11.2
通讯作者：
Kurre, Peter
中科院分区：
文献类型：
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作者：
Huan, Jianya;Hornick, Noah I.;Kurre, Peter
急性髓细胞白血病（AML）微环境中的外源性信号传导线索有助于疾病进展和治疗耐药性。然而，它仍然是未知的骨髓生态位，其中AML的出现是如何被颠覆，以支持白血病的持久性，在牺牲稳态功能。外泌体是细胞膜衍生的囊泡，其携带蛋白质和RNA货物，这些货物已经作为细胞-细胞通信的介质出现。在这项研究中，我们研究了外泌体在骨髓微环境的AML生态位发展中的作用，研究了它们的生物起源，重点是RNA运输。我们发现原代AML和AML细胞系都释放了外泌体大小的囊泡，这些囊泡进入旁观者细胞。这些外泌体富含与AML发病机制相关的几种编码和非编码RNA。此外，骨髓基质细胞对它们的摄取改变了它们的生长因子分泌。概念验证研究为转移RNA的典型功能提供了额外的证据。总之，我们的研究结果表明，AML外泌体运输改变了共培养的基质和造血祖细胞系的增殖，血管生成和迁移反应，有助于解释微环境生态位如何在AML入侵骨髓期间重新编程。Cancer Res; 73（2）; 918-29. (c)2012年AACR。
Extrinsic signaling cues in the microenvironment of acute myelogenous leukemia (AML) contribute to disease progression and therapy resistance. Yet, it remains unknown how the bone marrow niche in which AML arises is subverted to support leukemic persistence at the expense of homeostatic function. Exosomes are cell membrane-derived vesicles carrying protein and RNA cargoes that have emerged as mediators of cell-cell communication. In this study, we examined the role of exosomes in developing the AML niche of the bone marrow microenvironment, investigating their biogenesis with a focus on RNA trafficking. We found that both primary AML and AML cell lines released exosome-sized vesicles that entered bystander cells. These exosomes were enriched for several coding and noncoding RNAs relevant to AML pathogenesis. Furthermore, their uptake by bone marrow stromal cells altered their secretion of growth factors. Proof-of-concept studies provided additional evidence for the canonical functions of the transferred RNA. Taken together, our findings revealed that AML exosome trafficking alters the proliferative, angiogenic, and migratory responses of cocultured stromal and hematopoietic progenitor cell lines, helping explain how the microenvironmental niche becomes reprogrammed during invasion of the bone marrow by AML. Cancer Res; 73(2); 918-29. (c) 2012 AACR.