The role of exosomes and microRNAs in senescence and aging

Advanced Drug Delivery Reviews

Volumn 65, Issue 3, 2013, Pages 368-375

  Xu, Dan ^a,b   Tahara, Hidetoshi ^b  

^a DALIAN MARITIME UNIVERSITY   (China)

^b HIROSHIMA UNIVERSITY   (Japan)

Author keywords

Age associated disease; Aging; Exosome; MicroRNA; Senescence; Tumor suppression

Indexed keywords

BIOLOGICAL PROCESS; CELLULAR SENESCENCE; EXOSOME; INFORMATION TRANSFERS; MICRORNAS; SENESCENCE; SIGNALING PATHWAYS; TUMOR SUPPRESSION;

AGING OF MATERIALS; CELLS; GENE EXPRESSION; RNA; TISSUE;

CYTOLOGY;

BMI1 PROTEIN; CYCLIN A; CYCLIN DEPENDENT KINASE; CYCLIN DEPENDENT KINASE 4; CYCLIN DEPENDENT KINASE 6; CYCLIN E; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; MICRORNA; MICRORNA 138; MICRORNA 20A; MICRORNA 21; MICRORNA 22; MICRORNA 24; MICRORNA 29; MICRORNA 30; MYC PROTEIN; OCTAMER TRANSCRIPTION FACTOR 4; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN P16; PROTEIN P21; PROTEIN P53; RAS PROTEIN; SIRTUIN 1; UNCLASSIFIED DRUG; UNTRANSLATED RNA;

CELL AGING; CELL COMMUNICATION; CELL CONTACT; CELL CYCLE ARREST; CELL CYCLE PROGRESSION; CELL DIFFERENTIATION; CELL FUNCTION; CELL PROLIFERATION; CELL RENEWAL; DNA METHYLATION; ENDOCYTOSIS; EPIGENETICS; EXOSOME; HISTONE MODIFICATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SENESCENCE; SIGNAL TRANSDUCTION; TUMOR GROWTH; UPREGULATION;

AGING; ANIMALS; CELL AGING; EXOSOMES; GENE EXPRESSION REGULATION; HUMANS; MICRORNAS; SIGNAL TRANSDUCTION;

EID: 84874957751     PISSN: 0169409X     EISSN: 18728294     Source Type: Journal    
DOI: 10.1016/j.addr.2012.07.010     Document Type: Review

References (98)

1. Thery C., Zitvogel L., Amigorena S. Exosomes: composition, biogenesis and function. Nat. Rev. Immunol. 2002, 2:569-579.
2. Mathivanan S., Ji H., Simpson R.J. Exosomes: extracellular organelles important in intercellular communication. J. Proteomics 2010, 73:1907-1920.
3. Ratajczak J., Wysoczynski M., Hayek F., Janowska-Wieczorek A., Ratajczak M.Z. Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia 2006, 20:1487-1495.
4. Simpson R.J., Lim J.W., Moritz R.L., Mathivanan S. Exosomes: proteomic insights and diagnostic potential. Expert Rev. Proteomics 2009, 6:267-283.
5. Record M., Subra C., Silvente-Poirot S., Poirot M. Exosomes as intercellular signalosomes and pharmacological effectors. Biochem. Pharmacol. 2011, 81:1171-1182.
6. Thery C., Ostrowski M., Segura E. Membrane vesicles as conveyors of immune responses. Nat. Rev. Immunol. 2009, 9:581-593.
7. Al-Nedawi K., Meehan B., Rak J. Microvesicles: messengers and mediators of tumor progression. Cell Cycle 2009, 8:2014-2018.
8. Stoorvogel W., Kleijmeer M.J., Geuze H.J., Raposo G. The biogenesis and functions of exosomes. Traffic 2002, 3:321-330.
9. Bartel D.P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116:281-297.
10. Bushati N., Cohen S.M. microRNA functions. Annu. Rev. Cell Dev. Biol. 2007, 23:175-205.
11. Kosaka N., Iguchi H., Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010, 101:2087-2092.
12. Chen X., Ba Y., Ma L., Cai X., Yin Y., Wang K., Guo J., Zhang Y., Chen J., Guo X., Li Q., Li X., Wang W., Wang J., Jiang X., Xiang Y., Xu C., Zheng P., Zhang J., Li R., Zhang H., Shang X., Gong T., Ning G., Zen K., Zhang C.Y. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008, 18:997-1006.
13. Valadi H., Ekstrom K., Bossios A., Sjostrand M., Lee J.J., Lotvall J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 2007, 9:654-659.
14. Ohshima K., Inoue K., Fujiwara A., Hatakeyama K., Kanto K., Watanabe Y., Muramatsu K., Fukuda Y., Ogura S., Yamaguchi K., Mochizuki T. Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PLoS One 2010, 5:e13247.
15. Pitto L., Rizzo M., Simili M., Colligiani D., Evangelista M., Mercatanti A., Mariani L., Cremisi F., Rainaldi G. MiR-290 acts as a physiological effector of senescence in mouse embryo fibroblasts. Physiol. Genomics 2009, 39:210-218.
16. Poliseno L., Pitto L., Simili M., Mariani L., Riccardi L., Ciucci A., Rizzo M., Evangelista M., Mercatanti A., Pandolfi P.P., Rainaldi G. The proto-oncogene LRF is under post-transcriptional control of MiR-20a: implications for senescence. PLoS One 2008, 3:e2542.
17. Xu D., Takeshita F., Hino Y., Fukunaga S., Kudo Y., Tamaki A., Matsunaga J., Takahashi R.U., Takata T., Shimamoto A., Ochiya T., Tahara H. miR-22 represses cancer progression by inducing cellular senescence. J. Cell Biol. 2011, 193:409-424.
18. Tazawa H., Tsuchiya N., Izumiya M., Nakagama H. Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:15472-15477.
19. Lehmann B.D., Paine M.S., Brooks A.M., McCubrey J.A., Renegar R.H., Wang R., Terrian D.M. Senescence-associated exosome release from human prostate cancer cells. Cancer Res. 2008, 68:7864-7871.
20. Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. 1965, 37:614-636.
21. Campisi J., d'Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat. Rev. Mol. Cell Biol. 2007, 8:729-740.
22. Dimri G.P., Lee X., Basile G., Acosta M., Scott G., Roskelley C., Medrano E.E., Linskens M., Rubelj I., Pereira-Smith O., et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl. Acad. Sci. U. S. A. 1995, 92:9363-9367.
23. Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 2005, 120:513-522.
24. Vaziri H., Dessain S.K., Ng Eaton E., Imai S.I., Frye R.A., Pandita T.K., Guarente L., Weinberg R.A. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 2001, 107:149-159.
25. Sherr C.J., McCormick F. The RB and p53 pathways in cancer. Cancer Cell 2002, 2:103-112.
26. Brown J.P., Wei W., Sedivy J.M. Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. Science 1997, 277:831-834.
27. Borgdorff V., Lleonart M.E., Bishop C.L., Fessart D., Bergin A.H., Overhoff M.G., Beach D.H. Multiple microRNAs rescue from Ras-induced senescence by inhibiting p21(Waf1/Cip1). Oncogene 2010, 29:2262-2271.
28. Olsen C.L., Gardie B., Yaswen P., Stampfer M.R. Raf-1-induced growth arrest in human mammary epithelial cells is p16-independent and is overcome in immortal cells during conversion. Oncogene 2002, 21:6328-6339.
29. Sherr C.J., Roberts J.M. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999, 13:1501-1512.
30. Ruas M., Gregory F., Jones R., Poolman R., Starborg M., Rowe J., Brookes S., Peters G. CDK4 and CDK6 delay senescence by kinase-dependent and p16INK4a-independent mechanisms. Mol. Cell. Biol. 2007, 27:4273-4282.
31. Stein G.H., Drullinger L.F., Soulard A., Dulic V. Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. Mol. Cell. Biol. 1999, 19:2109-2117.
32. Simboeck E., Ribeiro J.D., Teichmann S., Di Croce L. Epigenetics and senescence: learning from the INK4-ARF locus. Biochem. Pharmacol. 2011, 82:1361-1370.
33. Dietrich N., Bracken A.P., Trinh E., Schjerling C.K., Koseki H., Rappsilber J., Helin K., Hansen K.H. Bypass of senescence by the polycomb group protein CBX8 through direct binding to the INK4A-ARF locus. EMBO J. 2007, 26:1637-1648.
34. Robert M.F., Morin S., Beaulieu N., Gauthier F., Chute I.C., Barsalou A., MacLeod A.R. DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Nat. Genet. 2003, 33:61-65.
35. Fang J.Y., Yang L., Zhu H.Y., Chen Y.X., Lu J., Lu R., Cheng Z.H., Xiao S.D. 5-Aza-2'-deoxycitydine induces demethylation and up-regulates transcription of p16INK4A gene in human gastric cancer cell lines. Chin. Med. J. (Engl) 2004, 117:99-103.
36. Lin T.S., Lee H., Chen R.A., Ho M.L., Lin C.Y., Chen Y.H., Tsai Y.Y., Chou M.C., Cheng Y.W. An association of DNMT3b protein expression with P16INK4a promoter hypermethylation in non-smoking female lung cancer with human papillomavirus infection. Cancer Lett. 2005, 226:77-84.
37. Tong J.H., Ng D.C., Chau S.L., So K.K., Leung P.P., Lee T.L., Lung R.W., Chan M.W., Chan A.W., Lo K.W., To K.F. Putative tumour-suppressor gene DAB2 is frequently down regulated by promoter hypermethylation in nasopharyngeal carcinoma. BMC Cancer 2010, 10:253.
38. Wagner M., Brosch G., Zwerschke W., Seto E., Loidl P., Jansen-Durr P. Histone deacetylases in replicative senescence: evidence for a senescence-specific form of HDAC-2. FEBS Lett. 2001, 499:101-106.
39. Jeyapalan J.C., Sedivy J.M. Cellular senescence and organismal aging. Mech. Ageing Dev. 2008, 129:467-474.
40. Krtolica A., Parrinello S., Lockett S., Desprez P.Y., Campisi J. Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:12072-12077.
41. Campisi J. Cellular senescence as a tumor-suppressor mechanism. Trends Cell Biol. 2001, 11:S27-S31.
42. Ohtani N., Mann D.J., Hara E. Cellular senescence: its role in tumor suppression and aging. Cancer Sci. 2009, 100:792-797.
43. Campisi J. Aging and cancer cell biology, 2008. Aging Cell 2008, 7:281-284.
44. Yamakuchi M., Lowenstein C.J. MiR-34, SIRT1 and p53: the feedback loop. Cell Cycle 2009, 8:712-715.
45. Sun F., Fu H., Liu Q., Tie Y., Zhu J., Xing R., Sun Z., Zheng X. Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest. FEBS Lett. 2008, 582:1564-1568.
46. Lal A., Kim H.H., Abdelmohsen K., Kuwano Y., Pullmann R., Srikantan S., Subrahmanyam R., Martindale J.L., Yang X., Ahmed F., Navarro F., Dykxhoorn D., Lieberman J., Gorospe M. p16(INK4a) translation suppressed by miR-24. PLoS One 2008, 3:e1864.
47. Takahashi Y., Forrest A.R., Maeno E., Hashimoto T., Daub C.O., Yasuda J. MiR-107 and MiR-185 can induce cell cycle arrest in human non small cell lung cancer cell lines. PLoS One 2009, 4:e6677.
48. Liu Q., Fu H., Sun F., Zhang H., Tie Y., Zhu J., Xing R., Sun Z., Zheng X. miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes. Nucleic Acids Res. 2008, 36:5391-5404.
49. Mitomo S., Maesawa C., Ogasawara S., Iwaya T., Shibazaki M., Yashima-Abo A., Kotani K., Oikawa H., Sakurai E., Izutsu N., Kato K., Komatsu H., Ikeda K., Wakabayashi G., Masuda T. Downregulation of miR-138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines. Cancer Sci. 2008, 99:280-286.
50. Venkataraman S., Alimova I., Fan R., Harris P., Foreman N., Vibhakar R. MicroRNA 128a increases intracellular ROS level by targeting Bmi-1 and inhibits medulloblastoma cancer cell growth by promoting senescence. PLoS One 2010, 5:e10748.
51. Christoffersen N.R., Shalgi R., Frankel L.B., Leucci E., Lees M., Klausen M., Pilpel Y., Nielsen F.C., Oren M., Lund A.H. p53-independent upregulation of miR-34a during oncogene-induced senescence represses MYC. Cell Death Differ. 2010, 17:236-245.
52. Voorhoeve P.M., le Sage C., Schrier M., Gillis A.J., Stoop H., Nagel R., Liu Y.P., van Duijse J., Drost J., Griekspoor A., Zlotorynski E., Yabuta N., De Vita G., Nojima H., Looijenga L.H., Agami R. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell 2006, 124:1169-1181.
53. Ren J., Zhu D., Liu M., Sun Y., Tian L. Downregulation of miR-21 modulates Ras expression to promote apoptosis and suppress invasion of Laryngeal squamous cell carcinoma. Eur. J. Cancer 2010, 46:3409-3416.
54. Meng F., Henson R., Lang M., Wehbe H., Maheshwari S., Mendell J.T., Jiang J., Schmittgen T.D., Patel T. Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology 2006, 130:2113-2129.
55. Barroso-del Jesus A., Lucena-Aguilar G., Menendez P. The miR-302-367 cluster as a potential stemness regulator in ESCs. Cell Cycle 2009, 8:394-398.
56. Nishino J., Kim I., Chada K., Morrison S.J. Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf Expression. Cell 2008, 135:227-239.
57. Bhaumik D., Scott G.K., Schokrpur S., Patil C.K., Orjalo A.V., Rodier F., Lithgow G.J., Campisi J. MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8. Aging (Albany NY) 2009, 1:402-411.
58. Martinez I., Cazalla D., Almstead L.L., Steitz J.A., DiMaio D. miR-29 and miR-30 regulate B-Myb expression during cellular senescence. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:522-527.
59. Pandey D.P., Picard D. miR-22 inhibits estrogen signaling by directly targeting the estrogen receptor alpha mRNA. Mol. Cell. Biol. 2009, 29:3783-3790.
60. Scott G.K., Goga A., Bhaumik D., Berger C.E., Sullivan C.S., Benz C.C. Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J. Biol. Chem. 2007, 282:1479-1486.
61. Davalos A.R., Coppe J.P., Campisi J., Desprez P.Y. Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis Rev. 2010, 29:273-283.
62. Coppe J.P., Patil C.K., Rodier F., Sun Y., Munoz D.P., Goldstein J., Nelson P.S., Desprez P.Y., Campisi J. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 2008, 6:2853-2868.
63. Kuilman T., Peeper D.S. Senescence-messaging secretome: SMS-ing cellular stress. Nat. Rev. Cancer 2009, 9:81-94.
64. Kuilman T., Michaloglou C., Vredeveld L.C., Douma S., van Doorn R., Desmet C.J., Aarden L.A., Mooi W.J., Peeper D.S. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 2008, 133:1019-1031.
65. Ancrile B., Lim K.H., Counter C.M. Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev. 2007, 21:1714-1719.
66. Huang S.S., Leal S.M., Chen C.L., Liu I.H., Huang J.S. Identification of insulin receptor substrate proteins as key molecules for the TbetaR-V/LRP-1-mediated growth inhibitory signaling cascade in epithelial and myeloid cells. FASEB J. 2004, 18:1719-1721.
67. Yang G., Rosen D.G., Zhang Z., Bast R.C., Mills G.B., Colacino J.A., Mercado-Uribe I., Liu J. The chemokine growth-regulated oncogene 1 (Gro-1) links RAS signaling to the senescence of stromal fibroblasts and ovarian tumorigenesis. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:16472-16477.
68. Cocucci E., Racchetti G., Meldolesi J. Shedding microvesicles: artefacts no more. Trends Cell Biol. 2009, 19:43-51.
69. Narita M., Nunez S., Heard E., Lin A.W., Hearn S.A., Spector D.L., Hannon G.J., Lowe S.W. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 2003, 113:703-716.
70. Al-Nedawi K., Meehan B., Kerbel R.S., Allison A.C., Rak J. Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:3794-3799.
71. Yu X., Harris S.L., Levine A.J. The regulation of exosome secretion: a novel function of the p53 protein. Cancer Res. 2006, 66:4795-4801.
72. Kirman I., Poltoratskaia N., Sylla P., Whelan R.L. Insulin-like growth factor-binding protein 3 inhibits growth of experimental colocarcinoma. Surgery 2004, 136:205-209.
73. Lespagnol A., Duflaut D., Beekman C., Blanc L., Fiucci G., Marine J.C., Vidal M., Amson R., Telerman A. Exosome secretion, including the DNA damage-induced p53-dependent secretory pathway, is severely compromised in TSAP6/Steap3-null mice. Cell Death Differ. 2008, 15:1723-1733.
74. Yu X., Riley T., Levine A.J. The regulation of the endosomal compartment by p53 the tumor suppressor gene. FEBS J. 2009, 276:2201-2212.
75. Feng Z. p53 regulation of the IGF-1/AKT/mTOR pathways and the endosomal compartment. Cold Spring Harb. Perspect. Biol. 2010, 2:a001057.
76. Volonte D., Zhang K., Lisanti M.P., Galbiati F. Expression of caveolin-1 induces premature cellular senescence in primary cultures of murine fibroblasts. Mol. Biol. Cell 2002, 13:2502-2517.
77. Linge A., Weinhold K., Blasche R., Kasper M., Barth K. Downregulation of caveolin-1 affects bleomycin-induced growth arrest and cellular senescence in A549 cells. Int. J. Biochem. Cell Biol. 2007, 39:1964-1974.
78. Campisi J. Cancer, aging and cellular senescence. In Vivo 2000, 14:183-188.
79. Lafferty-Whyte K., Cairney C.J., Jamieson N.B., Oien K.A., Keith W.N. Pathway analysis of senescence-associated miRNA targets reveals common processes to different senescence induction mechanisms. Biochim. Biophys. Acta 2009, 1792:341-352.
80. Dhahbi J.M., Atamna H., Boffelli D., Magis W., Spindler S.R., Martin D.I. Deep sequencing reveals novel microRNAs and regulation of microRNA expression during cell senescence. PLoS One 2011, 6:e20509.
81. Suh W.K., Gajewska B.U., Okada H., Gronski M.A., Bertram E.M., Dawicki W., Duncan G.S., Bukczynski J., Plyte S., Elia A., Wakeham A., Itie A., Chung S., Da Costa J., Arya S., Horan T., Campbell P., Gaida K., Ohashi P.S., Watts T.H., Yoshinaga S.K., Bray M.R., Jordana M., Mak T.W. The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses. Nat. Immunol. 2003, 4:899-906.
82. Yang M., Chen J., Su F., Yu B., Lin L., Liu Y., Huang J.D., Song E. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells. Mol. Cancer 2011, 10:117.
83. Leiszter K., Galamb O., Sipos F., Toth K., Valcz G., Patai V.A., Molnar J., Molnar B., Tulassay Z. Age-related microscopic and molecular changes of the human colon, and their role in the development of colorectal cancer in elderly people. Orv. Hetil. 2010, 151:885-892.
84. Wang A.L., Lukas T.J., Yuan M., Du N., Tso M.O., Neufeld A.H. Autophagy and exosomes in the aged retinal pigment epithelium: possible relevance to drusen formation and age-related macular degeneration. PLoS One 2009, 4:e4160.
85. Rajendran L., Honsho M., Zahn T.R., Keller P., Geiger K.D., Verkade P., Simons K. Alzheimer's disease beta-amyloid peptides are released in association with exosomes. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:11172-11177.
86. Fevrier B., Vilette D., Laude H., Raposo G. Exosomes: a bubble ride for prions?. Traffic 2005, 6:10-17.
87. Porto-Carreiro I., Fevrier B., Paquet S., Vilette D., Raposo G. Prions and exosomes: from PrPc trafficking to PrPsc propagation. Blood Cells Mol. Dis. 2005, 35:143-148.
88. Alais S., Simoes S., Baas D., Lehmann S., Raposo G., Darlix J.L., Leblanc P. Mouse neuroblastoma cells release prion infectivity associated with exosomal vesicles. Biology of the cell/ under the auspices of the European Cell Biology Organization 2008, 100:603-615.
89. Turchinovich A., Weiz L., Langheinz A., Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res. 2011, 39:7223-7233.
90. Arroyo J.D., Chevillet J.R., Kroh E.M., Ruf I.K., Pritchard C.C., Gibson D.F., Mitchell P.S., Bennett C.F., Pogosova-Agadjanyan E.L., Stirewalt D.L., Tait J.F., Tewari M. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:5003-5008.
91. Vickers K.C., Palmisano B.T., Shoucri B.M., Shamburek R.D., Remaley A.T. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat. Cell Biol. 2011, 13:423-433.
92. Taylor D.D., Zacharias W., Gercel-Taylor C. Exosome isolation for proteomic analyses and RNA profiling. Methods Mol. Biol. 2011, 728:235-246.
93. Ostrowski M., Carmo N.B., Krumeich S., Fanget I., Raposo G., Savina A., Moita C.F., Schauer K., Hume A.N., Freitas R.P., Goud B., Benaroch P., Hacohen N., Fukuda M., Desnos C., Seabra M.C., Darchen F., Amigorena S., Moita L.F., Thery C. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol. 2010, 12:19-30.
94. Riteau B., Faure F., Menier C., Viel S., Carosella E.D., Amigorena S., Rouas-Freiss N. Exosomes bearing HLA-G are released by melanoma cells. Hum. Immunol. 2003, 64:1064-1072.
95. Gesierich S., Berezovskiy I., Ryschich E., Zoller M. Systemic induction of the angiogenesis switch by the tetraspanin D6.1A/CO-029. Cancer Res. 2006, 66:7083-7094.
96. Kim J.W., Wieckowski E., Taylor D.D., Reichert T.E., Watkins S., Whiteside T.L. Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clin. Cancer Res. 2005, 11:1010-1020.
97. Gallo A., Tandon M., Alevizos I., Illei G.G. The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS One 2012, 7:e30679.
98. Alvarez-Erviti L., Seow Y., Yin H., Betts C., Lakhal S., Wood M.J. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 2011, 29:341-345.