RNA Trafficking by Acute Myelogenous Leukemia Exosomes

被引:220
作者
Huan, Jianya [1 ,4 ]
Hornick, Noah I. [1 ,4 ]
Shurtleff, Matthew J. [1 ]
Skinner, Amy M. [1 ,4 ]
Goloviznina, Natalya A. [1 ,4 ]
Roberts, Charles T., Jr. [1 ,2 ,3 ,5 ]
Kurre, Peter [1 ,4 ]
机构
[1] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97239 USA
[2] Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Portland, OR 97239 USA
[3] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA
[4] Oregon Hlth & Sci Univ, Pape Family Pediat Res Inst, Portland, OR 97239 USA
[5] Oregon Natl Primate Res Ctr, Beaverton, OR USA
关键词
ACUTE MYELOID-LEUKEMIA; FACTOR-I RECEPTOR; HORIZONTAL TRANSFER; ENDOTHELIAL-CELLS; CANCER PATIENTS; MESSENGER-RNA; MICROVESICLES; GROWTH; AML; FIBROBLASTS;
D O I
10.1158/0008-5472.CAN-12-2184
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:918 / 929
页数:12
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