Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis

Sonia A. Melo; Hikaru Sugimoto; Joyce T. O'Connell; Noritoshi Kato; Alberto Villanueva; August Vidal; Le Qiu; Edward Vitkin; Lev T. Perelman; Carlos A. Melo; Anthony Lucci; Cristina Ivan; George A. Calin; Raghu Kalluri

doi:10.1016/j.ccell.2014.09.005

Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis

Sonia A. Melo, Hikaru Sugimoto, Joyce T. O'Connell, Noritoshi Kato, Alberto Villanueva, August Vidal, Le Qiu, Edward Vitkin, Lev T. Perelman, Carlos A. Melo, Anthony Lucci, Cristina Ivan, George A. Calin, Raghu Kalluri

Research output: Contribution to journal › Article › peer-review

1236 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	707-721
Number of pages	15
Journal	Cancer cell
Volume	26
Issue number	5
DOIs	https://doi.org/10.1016/j.ccell.2014.09.005
State	Published - Nov 10 2014

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccell.2014.09.005

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title = "Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis",

abstract = "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.",

author = "Melo, {Sonia A.} and Hikaru Sugimoto and O'Connell, {Joyce T.} and Noritoshi Kato and Alberto Villanueva and August Vidal and Le Qiu and Edward Vitkin and Perelman, {Lev T.} and Melo, {Carlos A.} and Anthony Lucci and Cristina Ivan and Calin, {George A.} and Raghu Kalluri",

note = "Publisher Copyright: {\textcopyright} 2014 Elsevier Inc.",

year = "2014",

month = nov,

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doi = "10.1016/j.ccell.2014.09.005",

language = "English (US)",

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AU - Melo, Sonia A.

AU - Sugimoto, Hikaru

AU - O'Connell, Joyce T.

AU - Kato, Noritoshi

AU - Villanueva, Alberto

AU - Vidal, August

AU - Qiu, Le

AU - Vitkin, Edward

AU - Perelman, Lev T.

AU - Melo, Carlos A.

AU - Lucci, Anthony

AU - Ivan, Cristina

AU - Calin, George A.

AU - Kalluri, Raghu

PY - 2014/11/10

Y1 - 2014/11/10

N2 - 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.

AB - 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.

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SN - 1535-6108

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JO - Cancer cell

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Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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