Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis

被引：1644

作者：

Melo, Sonia A. ^{[1
,2
,3
]}

Sugimoto, Hikaru ^{[1
,2
,3
]}

O'Connell, Joyce T. ^{[2
,3
]}

Kato, Noritoshi ^{[2
,3
]}

Villanueva, Alberto ^{[4
]}

Vidal, August ^{[5
]}

Qiu, Le ^{[6
,7
]}

Vitkin, Edward ^{[6
,7
]}

Perelman, Lev T. ^{[6
,7
]}

Melo, Carlos A. ^{[8
,9
]}

Lucci, Anthony ^{[10
]}

Ivan, Cristina ^{[11
]}

Calin, George A. ^{[12
]}

Kalluri, Raghu ^{[1
,2
,3
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Metastasis Res Ctr, Dept Canc Biol, Houston, TX 77054 USA

[2] Beth Israel Deaconess Med Ctr, Dept Med, Div Matrix Biol, Boston, MA 02215 USA

[3] Harvard Univ, Sch Med, Boston, MA 02215 USA

[4] Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol, Translat Res Lab, Barcelona 08908, Spain

[5] Bellvitge Biomed Res Inst IDIBELL, Hosp Univ Bellvitge, Dept Pathol, Barcelona 08908, Spain

[6] Beth Israel Deaconess Med Ctr, Dept Obstet Gynecol & Reprod Biol, Ctr Adv Biomed Imaging & Photon, Boston, MA 02215 USA

[7] Beth Israel Deaconess Med Ctr, Dept Med, Ctr Adv Biomed Imaging & Photon, Boston, MA 02215 USA

[8] Netherlands Canc Inst, Div Gene Regulat, NL-1066 CX Amsterdam, Netherlands

[9] Ctr Neurosci & Cell Biol, Doctoral Programme Biomed & Expt Biol, P-3004517 Coimbra, Portugal

[10] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA

[11] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNAs, Houston, TX 77054 USA

[12] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77054 USA

来源：

CANCER CELL | 2014年 / 26卷 / 05期

基金：

美国国家科学基金会;

关键词：

CONFOCAL LIGHT-ABSORPTION; MECHANISM; ENDOSOMES; PROTEINS; EXCHANGE; DICER; TRBP; RNA;

D O I：

10.1016/j.ccell.2014.09.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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 exosonnes 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.

引用

页码：707 / 721

页数：15

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