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Biogenesis and Functions of Exosomes and Extracellular Vesicles

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Lentiviral Vectors and Exosomes as Gene and Protein Delivery Tools

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1448))

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Abstract

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Research on extracellular vesicles (EVs) is a new and emerging field that is rapidly growing. Many features of these structures still need to be described and discovered. This concerns their biogenesis, their release and cellular entrance mechanisms, as well as their functions, particularly in vivo. Hence our knowledge on EV is constantly evolving and sometimes changing. In our review we summarize the most important facts of our current knowledge about extracellular vesicles and described some of the assumed functions in the context of cancer and HIV infection.

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References

  1. Skog J et al (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10:1470–1476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Muratori C et al (2009) Massive secretion by T cells is caused by HIV Nef in infected cells and by Nef transfer to bystander cells. Cell Host Microbe 6:218–230

    Article  CAS  PubMed  Google Scholar 

  3. Bollati V et al (2014) Susceptibility to particle health effects, miRNA and exosomes: rationale and study protocol of the SPHERE study. BMC Public Health 14:1137

    Article  PubMed  PubMed Central  Google Scholar 

  4. Trams EG et al (1981) Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta 645:63–70

    Article  CAS  PubMed  Google Scholar 

  5. Harding C, Heuser J, Stahl P (1983) Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol 97:329–339

    Article  CAS  PubMed  Google Scholar 

  6. Pan BT et al (1985) Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J Cell Biol 101:942–948

    Article  CAS  PubMed  Google Scholar 

  7. Skokos D et al (2001) Mast cell-dependent B and T lymphocyte activation is mediated by the secretion of immunologically active exosomes. J Immunol 166:868–876

    Article  CAS  PubMed  Google Scholar 

  8. Wolfers J et al (2001) Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med 7:297–303

    Article  CAS  PubMed  Google Scholar 

  9. Kadiu I et al (2012) Biochemical and biologic characterization of exosomes and microvesicles as facilitators of HIV-1 infection in macrophages. J Immunol 189:744–754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Li J et al (2013) Exosomes mediate the cell-to-cell transmission of IFN-alpha-induced antiviral activity. Nat Immunol 14:793–803

    Article  CAS  PubMed  Google Scholar 

  11. Chatila TA, Williams CB (2014) Regulatory T cells: exosomes deliver tolerance. Immunity 41:3–5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Poteryaev D et al (2010) Identification of the switch in early-to-late endosome transition. Cell 141:497–508

    Article  CAS  PubMed  Google Scholar 

  13. Thery C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2:569–579

    CAS  PubMed  Google Scholar 

  14. Williams RL, Urbe S (2007) The emerging shape of the ESCRT machinery. Nat Rev Mol Cell Biol 8:355–368

    Article  CAS  PubMed  Google Scholar 

  15. Rusten TE, Vaccari T, Stenmark H (2012) Shaping development with ESCRTs. Nat Cell Biol 14:38–45

    Article  CAS  Google Scholar 

  16. Hurley JH, Hanson PI (2010) Membrane budding and scission by the ESCRT machinery: it’s all in the neck. Nat Rev Mol Cell Biol 11:556–566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Robbins PD, Morelli AE (2014) Regulation of immune responses by extracellular vesicles. Nat Rev Immunol 14:195–208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Trajkovic K et al (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319:1244–1247

    Article  CAS  PubMed  Google Scholar 

  19. Wu BX, Clarke CJ, Hannun YA (2010) Mammalian neutral sphingomyelinases: regulation and roles in cell signaling responses. Neuromolecular Med 12:320–330

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kharaziha P et al (2012) Tumor cell-derived exosomes: a message in a bottle. Biochim Biophys Acta 1826:103–111

    CAS  PubMed  Google Scholar 

  21. Ostrowski M et al (2010) Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 12:19–30; sup pp 11–13

    Google Scholar 

  22. Hsu C et al (2010) Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C. J Cell Biol 189:223–232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Fader CM et al (2009) TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. Biochim Biophys Acta 1793:1901–1916

    Article  CAS  PubMed  Google Scholar 

  24. Zitvogel L et al (1998) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med 4:594–600

    Article  CAS  PubMed  Google Scholar 

  25. Bhatnagar S et al (2007) Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo. Blood 110:3234–3244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Raposo G et al (1997) Accumulation of major histocompatibility complex class II molecules in mast cell secretory granules and their release upon degranulation. Mol Biol Cell 8:2631–2645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Blanchard N et al (2002) TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex. J Immunol 168:3235–3241

    Article  CAS  PubMed  Google Scholar 

  28. Buschow SI et al (2009) MHC II in dendritic cells is targeted to lysosomes or T cell-induced exosomes via distinct multivesicular body pathways. Traffic 10:1528–1542

    Article  CAS  PubMed  Google Scholar 

  29. Nolte-'t Hoen EN et al (2009) Activated T cells recruit exosomes secreted by dendritic cells via LFA-1. Blood 113:1977–1981

    Article  PubMed  Google Scholar 

  30. Muntasell A et al (2007) T cell-induced secretion of MHC class II-peptide complexes on B cell exosomes. EMBO J 26:4263–4272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lespagnol A et al (2008) Exosome secretion, including the DNA damage-induced p53-dependent secretory pathway, is severely compromised in TSAP6/Steap3-null mice. Cell Death Differ 15:1723–1733

    Article  CAS  PubMed  Google Scholar 

  32. Yu X, Harris SL, Levine AJ (2006) The regulation of exosome secretion: a novel function of the p53 protein. Cancer Res 66:4795–4801

    Article  CAS  PubMed  Google Scholar 

  33. Deolindo P, Evans-Osses I, Ramirez MI (2013) Microvesicles and exosomes as vehicles between protozoan and host cell communication. Biochem Soc Trans 41:252–257

    Article  CAS  PubMed  Google Scholar 

  34. Cocucci E, Racchetti G, Meldolesi J (2009) Shedding microvesicles: artefacts no more. Trends Cell Biol 19:43–51

    Article  CAS  PubMed  Google Scholar 

  35. Conde D et al (2005) Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 106:1604–1611

    Article  PubMed  Google Scholar 

  36. Quesenberry PJ, Aliotta JM (2010) Cellular phenotype switching and microvesicles. Adv Drug Deliv Rev 62:1141–1148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cocucci E et al (2007) Enlargeosome traffic: exocytosis triggered by various signals is followed by endocytosis, membrane shedding or both. Traffic 8:742–757

    Article  CAS  PubMed  Google Scholar 

  38. Balaj L et al (2011) Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat Commun 2:180

    Article  PubMed  PubMed Central  Google Scholar 

  39. Gutierrez-Vazquez C et al (2013) Transfer of extracellular vesicles during immune cell-cell interactions. Immunol Rev 251:125–142

    Article  PubMed  PubMed Central  Google Scholar 

  40. Thery C et al (1999) Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. J Cell Biol 147:599–610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mittelbrunn M et al (2011) Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun 2:282

    Article  PubMed  PubMed Central  Google Scholar 

  42. Hessvik NP et al (2012) Profiling of microRNAs in exosomes released from PC-3 prostate cancer cells. Biochim Biophys Acta 1819:1154–1163

    Article  CAS  PubMed  Google Scholar 

  43. Li CC et al (2013) Glioma microvesicles carry selectively packaged coding and non-coding RNAs which alter gene expression in recipient cells. RNA Biol 10:1333–1344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Gezer U et al (2014) Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes. Cell Biol Int 38:1076–1079

    CAS  PubMed  Google Scholar 

  45. Shen B et al (2011) Protein targeting to exosomes/microvesicles by plasma membrane anchors. J Biol Chem 286:14383–14395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Melo SA et al (2014) Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell 26:707–721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Villarroya-Beltri C et al (2013) Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat Commun 4:2980

    Article  PubMed  PubMed Central  Google Scholar 

  48. Koppers-Lalic D et al (2014) Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes. Cell Rep 8:1649–1658

    Article  CAS  PubMed  Google Scholar 

  49. Squadrito ML et al (2014) Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells. Cell Rep 8:1432–1446

    Article  CAS  PubMed  Google Scholar 

  50. Yuana Y et al (2013) Extracellular vesicles in physiological and pathological conditions. Blood Rev 27:31–39

    Article  CAS  PubMed  Google Scholar 

  51. Peinado H et al (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18:883–891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Alvarez-Erviti L et al (2011) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29:341–345

    Article  CAS  PubMed  Google Scholar 

  53. Thery C, Ostrowski M, Segura E (2009) Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9:581–593

    Article  CAS  PubMed  Google Scholar 

  54. Valadi H et al (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659

    Article  CAS  PubMed  Google Scholar 

  55. Al-Nedawi K et al (2008) Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 10:619–624

    Article  CAS  PubMed  Google Scholar 

  56. Montecalvo A et al (2012) Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 119:756–766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Biro E et al (2003) Human cell-derived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner. J Thromb Haemost 1:2561–2568

    Article  CAS  PubMed  Google Scholar 

  58. Zhang B et al (2015) HucMSC-exosome mediated-Wnt4 signaling is required for cutaneous wound healing. Stem Cells 33(7):2158–2168

    Google Scholar 

  59. Taylor DD, Akyol S, Gercel-Taylor C (2006) Pregnancy-associated exosomes and their modulation of T cell signaling. J Immunol 176:1534–1542

    Article  CAS  PubMed  Google Scholar 

  60. Saenz-Cuesta M, Osorio-Querejeta I, Otaegui D (2014) Extracellular vesicles in multiple sclerosis: what are they telling us? Front Cell Neurosci 8:100

    Article  PubMed  PubMed Central  Google Scholar 

  61. Buzas EI et al (2014) Emerging role of extracellular vesicles in inflammatory diseases. Nat Rev Rheumatol 10:356–364

    Article  CAS  PubMed  Google Scholar 

  62. Silverman JM, Reiner NE (2011) Exosomes and other microvesicles in infection biology: organelles with unanticipated phenotypes. Cell Microbiol 13:1–9

    Article  CAS  PubMed  Google Scholar 

  63. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  PubMed  Google Scholar 

  64. Andreola G et al (2002) Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. J Exp Med 195:1303–1316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Raisova M et al (2000) Resistance to CD95/Fas-induced and ceramide-mediated apoptosis of human melanoma cells is caused by a defective mitochondrial cytochrome c release. FEBS Lett 473:27–32

    Article  CAS  PubMed  Google Scholar 

  66. Irmler M et al (1997) Inhibition of death receptor signals by cellular FLIP. Nature 388:190–195

    Article  CAS  PubMed  Google Scholar 

  67. Delcayre A, Shu H, Le Pecq JB (2005) Dendritic cell-derived exosomes in cancer immunotherapy: exploiting nature's antigen delivery pathway. Expert Rev Anticancer Ther 5:537–547

    Article  CAS  PubMed  Google Scholar 

  68. Naslund TI et al (2013) Dendritic cell-derived exosomes need to activate both T and B cells to induce antitumor immunity. J Immunol 190:2712–2719

    Article  PubMed  Google Scholar 

  69. Sobo-Vujanovic A et al (2014) Dendritic-cell exosomes cross-present Toll-like receptor-ligands and activate bystander dendritic cells. Cell Immunol 289:119–127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Raposo G et al (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183:1161–1172

    Article  CAS  PubMed  Google Scholar 

  71. Morse MA et al (2005) A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J Transl Med 3:9

    Article  PubMed  PubMed Central  Google Scholar 

  72. Escudier B et al (2005) Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first phase I clinical trial. J Transl Med 3:10

    Article  PubMed  PubMed Central  Google Scholar 

  73. Viaud S et al (2009) Dendritic cell-derived exosomes promote natural killer cell activation and proliferation: a role for NKG2D ligands and IL-15Ralpha. PLoS One 4:e4942

    Article  PubMed  PubMed Central  Google Scholar 

  74. Munich S et al (2012) Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands. Oncoimmunology 1:1074–1083

    Article  PubMed  PubMed Central  Google Scholar 

  75. Lee JH et al (2013) HIV Nef, paxillin, and Pak1/2 regulate activation and secretion of TACE/ADAM10 proteases. Mol Cell 49:668–679

    Article  CAS  PubMed  Google Scholar 

  76. Arenaccio C et al (2014) Exosomes from human immunodeficiency virus type 1 (HIV-1)-infected cells license quiescent CD4+ T lymphocytes to replicate HIV-1 through a Nef- and ADAM17-dependent mechanism. J Virol 88:11529–11539

    Article  PubMed  PubMed Central  Google Scholar 

  77. Arenaccio C et al (2014) Cell activation and HIV-1 replication in unstimulated CD4+ T lymphocytes ingesting exosomes from cells expressing defective HIV-1. Retrovirology 11:46

    Article  PubMed  PubMed Central  Google Scholar 

  78. Taylor DD, Gercel-Taylor C (2008) MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 110:13–21

    Article  CAS  PubMed  Google Scholar 

  79. Ogata-Kawata H et al (2014) Circulating exosomal microRNAs as biomarkers of colon cancer. PLoS One 9:e92921

    Article  PubMed  PubMed Central  Google Scholar 

  80. Schorey JS, Bhatnagar S (2008) Exosome function: from tumor immunology to pathogen biology. Traffic 9:871–881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Azmi AS, Bao B, Sarkar FH (2013) Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev 32:623–642

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg, Hartmannstr. 14, 91054, Erlangen, Germany

    Florian Dreyer & Andreas Baur

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  1. Florian Dreyer
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  2. Andreas Baur
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Correspondence to Andreas Baur .

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  1. Istituto Superiore di Sanità, National AIDS Center, Rome, Italy

    Maurizio Federico

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Dreyer, F., Baur, A. (2016). Biogenesis and Functions of Exosomes and Extracellular Vesicles. In: Federico, M. (eds) Lentiviral Vectors and Exosomes as Gene and Protein Delivery Tools. Methods in Molecular Biology, vol 1448. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3753-0_15

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  • DOI: https://doi.org/10.1007/978-1-4939-3753-0_15

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3751-6

  • Online ISBN: 978-1-4939-3753-0

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