Melo Sonia A, Sugimoto Hikaru, O'Connell Joyce T, Kato Noritoshi, Villanueva Alberto, Vidal August, Qiu Le, Vitkin Edward, Perelman Lev T, Melo Carlos A, Lucci Anthony, Ivan Cristina, Calin George A, Kalluri Raghu
Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Cancer Cell. 2014 Nov 10;26(5):707-21. doi: 10.1016/j.ccell.2014.09.005. Epub 2014 Oct 23.
Exosomes are secreted by all cell types and contain proteins and nucleic acids. Here, we report that breast cancer associated exosomes contain microRNAs (miRNAs) associated with the RISC-Loading Complex (RLC) and display cell-independent capacity to process precursor microRNAs (pre-miRNAs) into mature miRNAs. Pre-miRNAs, along with Dicer, AGO2, and TRBP, are present in exosomes of cancer cells. CD43 mediates the accumulation of Dicer specifically in cancer exosomes. Cancer exosomes mediate an efficient and rapid silencing of mRNAs to reprogram the target cell transcriptome. Exosomes derived from cells and sera of patients with breast cancer instigate nontumorigenic epithelial cells to form tumors in a Dicer-dependent manner. These findings offer opportunities for the development of exosomes based biomarkers and therapies.
外泌体由所有细胞类型分泌,包含蛋白质和核酸。在此,我们报告乳腺癌相关外泌体含有与RNA诱导沉默复合体(RLC)相关的微小RNA(miRNA),并具有将前体微小RNA(pre-miRNA)加工成成熟miRNA的不依赖细胞的能力。Pre-miRNA与Dicer、AGO2和TRBP一起存在于癌细胞的外泌体中。CD43介导Dicer特异性在癌症外泌体中积累。癌症外泌体介导mRNA的高效快速沉默,以重新编程靶细胞转录组。源自乳腺癌患者细胞和血清的外泌体以Dicer依赖的方式促使非致瘤性上皮细胞形成肿瘤。这些发现为基于外泌体的生物标志物和疗法的开发提供了机会。