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.
authors.affiliation: 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.
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Melo
authors.affiliation: 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.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sugimoto
authors.affiliation: Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Joyce T
authors.initials: JT
authors.lastname: O'Connell
authors.affiliation: Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Kato
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona 08908, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Villanueva
authors.affiliation: Department of Pathology, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona 08908, Spain.
authors.forename: August
authors.initials: A
authors.lastname: Vidal
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Biology, and Department of Medicine, Center for Advanced Biomedical Imaging and Photonics, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Le
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Biology, and Department of Medicine, Center for Advanced Biomedical Imaging and Photonics, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Vitkin
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Biology, and Department of Medicine, Center for Advanced Biomedical Imaging and Photonics, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Lev T
authors.initials: LT
authors.lastname: Perelman
authors.affiliation: Division of Gene Regulation, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Doctoral Programme in Biomedicine and Experimental Biology, Centre for Neuroscience and Cell Biology, 3004-517 Coimbra, Portugal.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Melo
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Lucci
authors.affiliation: Center for RNA Interference and Non-coding RNAs, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ivan
authors.affiliation: Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.affiliation: 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. Electronic address: rkalluri@mdanderson.org.
authors.forename: Raghu
authors.initials: R
authors.lastname: Kalluri
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002268:Carboxypeptidases / Q000378:metabolism; D063646:Carcinogenesis / Q000378:metabolism*; D016022:Case-Control Studies; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D055354:Exosomes / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis*; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D059467:Transcriptome; D000099253:Trans-Activation Responsive RNA-Binding Protein
chemical_list: D060565:Argonaute Proteins; D002268:Carboxypeptidases; D053487:DEAD-box RNA Helicases; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D043244:Ribonuclease III; D000099253:Trans-Activation Responsive RNA-Binding Protein; C466422:AGO2 protein, human; C408087:DICER1 protein, human; C436327:SCPEP1 protein, human