Seminars in Immunopathology

, Volume 33, Issue 5, pp 455–467 | Cite as

Microvesicles as mediators of intercellular communication in cancer—the emerging science of cellular ‘debris’

  • Tae Hoon Lee
  • Esterina D’Asti
  • Nathalie Magnus
  • Khalid Al-Nedawi
  • Brian Meehan
  • Janusz Rak


Cancer cells emit a heterogeneous mixture of vesicular, organelle-like structures (microvesicles, MVs) into their surroundings including blood and body fluids. MVs are generated via diverse biological mechanisms triggered by pathways involved in oncogenic transformation, microenvironmental stimulation, cellular activation, stress, or death. Vesiculation events occur either at the plasma membrane (ectosomes, shed vesicles) or within endosomal structures (exosomes). MVs are increasingly recognized as mediators of intercellular communication due to their capacity to merge with and transfer a repertoire of bioactive molecular content (cargo) to recipient cells. Such processes may occur both locally and systemically, contributing to the formation of microenvironmental fields and niches. The bioactive cargo of MVs may include growth factors and their receptors, proteases, adhesion molecules, signalling molecules, as well as DNA, mRNA, and microRNA (miRs) sequences. Tumour cells emit large quantities of MVs containing procoagulant, growth regulatory and oncogenic cargo (oncosomes), which can be transferred throughout the cancer cell population and to non-transformed stromal cells, endothelial cells and possibly to the inflammatory infiltrates (oncogenic field effect). These events likely impact tumour invasion, angiogenesis, metastasis, drug resistance, and cancer stem cell hierarchy. Ongoing studies explore the molecular mechanisms and mediators of MV-based intercellular communication (cancer vesiculome) with the hope of using this information as a possible source of therapeutic targets and disease biomarkers in cancer.


Angiogenesis Biomarker Cancer Exosomes Intercellular communication Microvesicles Oncogenes 





Tissue factor


Epidermal growth factor receptor


Mutant EGFR (variant III)


Glioblastoma multiforme






Messenger ribonucleic acid




Receptor tyrosine kinase


Vascular endothelial growth factor


VEGF receptor 2



This work was supported by grants from the Canadian Cancer Society Research Institute (CCSRI) and Canadian Institutes of Health Research (CIHR) to J.R. who is a holder of the Jack Cole Chair in Pediatric Oncology at McGill University.




  1. 1.
    Citri A, Yarden Y (2006) EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol 7:505–516PubMedGoogle Scholar
  2. 2.
    Blume-Jensen P, Hunter T (2001) Oncogenic kinase signalling. Nature 411:355–365PubMedGoogle Scholar
  3. 3.
    Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak MZ (2006) Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia 20:1487–1495PubMedGoogle Scholar
  4. 4.
    Sherer NM, Mothes W (2008) Cytonemes and tunneling nanotubules in cell-cell communication and viral pathogenesis. Trends Cell Biol 18:414–420PubMedGoogle Scholar
  5. 5.
    Ahmed KA, Xiang J (2010) Mechanisms of cellular communication through intercellular protein transfer. J Cell Mol Med. doi: 10.1111/j.1582-4934.2010.01008.x
  6. 6.
    Thery C, Ostrowski M, Segura E (2009) Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9:581–593PubMedGoogle Scholar
  7. 7.
    Mathivanan S, Ji H, Simpson RJ (2010) Exosomes: extracellular organelles important in intercellular communication. J Proteomics 73:1907–1920PubMedGoogle Scholar
  8. 8.
    Caumartin J, Lemaoult J, Carosella ED (2006) Intercellular exchanges of membrane patches (trogocytosis) highlight the next level of immune plasticity. Transpl Immunol 17:20–22PubMedGoogle Scholar
  9. 9.
    Rak J (2010) Microparticles in cancer. Semin Thromb Hemost 36:888–906PubMedGoogle Scholar
  10. 10.
    Simons M, Raposo G (2009) Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol 21:575–581PubMedGoogle Scholar
  11. 11.
    Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L (2010) Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int 78:838–848PubMedGoogle Scholar
  12. 12.
    Muralidharan-Chari V, Clancy JW, Sedgwick A, Souza-Schorey C (2010) Microvesicles: mediators of extracellular communication during cancer progression. J Cell Sci 123:1603–1611PubMedGoogle Scholar
  13. 13.
    Pilzer D, Gasser O, Moskovich O, Schifferli JA, Fishelson Z (2005) Emission of membrane vesicles: roles in complement resistance, immunity and cancer. Springer Semin Immunopathol 27:375–387PubMedGoogle Scholar
  14. 14.
    Mause SF, Weber C (2010) Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res 107:1047–1057PubMedGoogle Scholar
  15. 15.
    Trams EG, Lauter CJ, Salem N Jr, Heine U (1981) Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta 645:63–70PubMedGoogle Scholar
  16. 16.
    Vindelov LL, Christensen IJ, Keiding N, Spang-Thomsen M, Nissen NI (1983) Long-term storage of samples for flow cytometric DNA analysis. Cytometry 3:317–322PubMedGoogle Scholar
  17. 17.
    Harding C, Heuser J, Stahl P (1983) Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol 97:329–339PubMedGoogle Scholar
  18. 18.
    Al-Nedawi K, Meehan B, Rak J (2009) Microvesicles: messengers and mediators of tumor progression. Cell Cycle 8:2014–2018PubMedGoogle Scholar
  19. 19.
    Bergsmedh A, Szeles A, Henriksson M et al (2001) Horizontal transfer of oncogenes by uptake of apoptotic bodies. Proc Natl Acad Sci USA 98:6407–6411PubMedGoogle Scholar
  20. 20.
    Wolf P (1967) The nature and significance of platelet products in human plasma. Br J Haematol 13:269–288PubMedGoogle Scholar
  21. 21.
    Lee T-H, Rak J (2011) Unpublished observation. Data fileGoogle Scholar
  22. 22.
    Simpson RJ, Lim JW, Moritz RL, Mathivanan S (2009) Exosomes: proteomic insights and diagnostic potential. Expert Rev Proteomics 6:267–283PubMedGoogle Scholar
  23. 23.
    Marzesco AM, Janich P, Wilsch-Brauninger M et al (2005) Release of extracellular membrane particles carrying the stem cell marker prominin-1 (CD133) from neural progenitors and other epithelial cells. J Cell Sci 118:2849–2858PubMedGoogle Scholar
  24. 24.
    Murphy JE, Padilla BE, Hasdemir B, Cottrell GS, Bunnett NW (2009) Endosomes: a legitimate platform for the signaling train. Proc Natl Acad Sci U S A 20(106):17615–17622Google Scholar
  25. 25.
    Del Conde I, Shrimpton CN, Thiagarajan P, Lopez JA (2005) Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 106:1604–1611PubMedGoogle Scholar
  26. 26.
    Hurley JH, Hanson PI (2010) Membrane budding and scission by the ESCRT machinery: it's all in the neck. Nat Rev Mol Cell Biol 11:556–566PubMedGoogle Scholar
  27. 27.
    Irion U, St JD (2007) bicoid RNA localization requires specific binding of an endosomal sorting complex. Nature 445:554–558PubMedGoogle Scholar
  28. 28.
    Lozano J, Morales A, Cremesti A et al (2001) Niemann-Pick disease versus acid sphingomyelinase deficiency. Cell Death Differ 8:100–103PubMedGoogle Scholar
  29. 29.
    Zhou Q, Zhao J, Wiedmer T, Sims PJ (2002) Normal hemostasis but defective hematopoietic response to growth factors in mice deficient in phospholipid scramblase 1. Blood 99:4030–4038PubMedGoogle Scholar
  30. 30.
    Piccin A, Murphy WG, Smith OP (2007) Circulating microparticles: pathophysiology and clinical implications. Blood Rev 21:157–171PubMedGoogle Scholar
  31. 31.
    Burnier L, Fontana P, Kwak BR, Ngelillo-Scherrer A (2009) Cell-derived microparticles in haemostasis and vascular medicine. Thromb Haemost 101:439–451PubMedGoogle Scholar
  32. 32.
    Bianco F, Perrotta C, Novellino L et al (2009) Acid sphingomyelinase activity triggers microparticle release from glial cells. EMBO J 28:1043–1054PubMedGoogle Scholar
  33. 33.
    Ray DM, Spinelli SL, Pollock SJ et al (2008) Peroxisome proliferator-activated receptor gamma and retinoid X receptor transcription factors are released from activated human platelets and shed in microparticles. Thromb Haemost 99:86–95PubMedGoogle Scholar
  34. 34.
    Millimaggi D, Mari M, D'Ascenzo S et al (2007) Tumor vesicle-associated CD147 modulates the angiogenic capability of endothelial cells. Neoplasia 9:349–357PubMedGoogle Scholar
  35. 35.
    Yu X, Harris SL, Levine AJ (2006) The regulation of exosome secretion: a novel function of the p53 protein. Cancer Res 66:4795–4801PubMedGoogle Scholar
  36. 36.
    Williams RL, Urbe S (2007) The emerging shape of the ESCRT machinery. Nat Rev Mol Cell Biol 8:355–368PubMedGoogle Scholar
  37. 37.
    Trajkovic K, Hsu C, Chiantia S et al (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319:1244–1247PubMedGoogle Scholar
  38. 38.
    Al-Nedawi K, Meehan B, Kerbel RS, Allison AC, Rak J (2009) Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR. Proc Natl Acad Sci U S A 106:3794–3799PubMedGoogle Scholar
  39. 39.
    Francis JI, Davila M, Robles-Carillo L, Amirkhosravi A (2010) Tissue factor-bearing microparticles released from tumor cells: relationship of particle size to procoagulant activity [abstract]. Thromb Res 125:S163Google Scholar
  40. 40.
    Pan BT, Teng K, Wu C, Adam M, Johnstone RM (1985) Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J Cell Biol 101:942–948PubMedGoogle Scholar
  41. 41.
    Johnstone RM (2006) Exosomes biological significance: a concise review. Blood Cells Mol Dis 36:315–321PubMedGoogle Scholar
  42. 42.
    Chairoungdua A, Smith DL, Pochard P, Hull M, Caplan MJ (2010) Exosome release of beta-catenin: a novel mechanism that antagonizes Wnt signaling. J Cell Biol 20(190):1079–1091Google Scholar
  43. 43.
    Ghosh AK, Secreto CR, Knox TR et al (2010) Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: implications for disease progression. Blood 115:1755–1764PubMedGoogle Scholar
  44. 44.
    Bebawy M, Combes V, Lee E et al (2009) Membrane microparticles mediate transfer of P-glycoprotein to drug sensitive cancer cells. Leukemia 23:1643–1649PubMedGoogle Scholar
  45. 45.
    Sheldon H, Heikamp E, Turley H et al (2010) New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes. Blood 116:2385–2394PubMedGoogle Scholar
  46. 46.
    Hendrix A, Westbroek W, Bracke M, De WO (2010) An ex(o)citing machinery for invasive tumor growth. Cancer Res 70:9533–9537PubMedGoogle Scholar
  47. 47.
    Zwicker JI (2010) Predictive value of tissue factor bearing microparticles in cancer associated thrombosis. Thromb Res 125:S89–S91PubMedGoogle Scholar
  48. 48.
    Albanese J, Meterissian S, Kontogiannea M et al (1998) Biologically active Fas antigen and its cognate ligand are expressed on plasma membrane-derived extracellular vesicles. Blood 91:3862–3874PubMedGoogle Scholar
  49. 49.
    Taraboletti G, D'Ascenzo S, Giusti I et al (2006) Bioavailability of VEGF in tumor-shed vesicles depends on vesicle burst induced by acidic pH. Neoplasia 8:96–103PubMedGoogle Scholar
  50. 50.
    Zhou Z (2007) New phosphatidylserine receptors: clearance of apoptotic cells and more. Dev Cell 13:759–760PubMedGoogle Scholar
  51. 51.
    Celi A, Lorenzet R, Furie BC, Furie B (2004) Microparticles and a P-selectin-mediated pathway of blood coagulation. Dis Markers 20:347–352PubMedGoogle Scholar
  52. 52.
    Tesselaar ME, Romijn FP, van der Linden IK et al (2007) Microparticle-associated tissue factor activity: a link between cancer and thrombosis? J Thromb Haemost 5:520–527PubMedGoogle Scholar
  53. 53.
    Mack M, Kleinschmidt A, Bruhl H et al (2000) Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection. Nat Med 6:769–775PubMedGoogle Scholar
  54. 54.
    Mause SF, von Hundelshausen P, Zernecke A, Koenen RR, Weber C (2005) Platelet microparticles: a transcellular delivery system for RANTES promoting monocyte recruitment on endothelium. Arterioscler Thromb Vasc Biol 25:1512–1518PubMedGoogle Scholar
  55. 55.
    Al-Nedawi K, Meehan B, Micaleff J, Guha A, Rak J (2010) Phosphoproteome of tumour derived microvesicles as a source of biomarkers to monitor the effects of targeted agents in glioblastoma [abstract]. Society of Neurooncology, Annual Meeting, MontrealGoogle Scholar
  56. 56.
    Taraboletti G, D'Ascenzo S, Borsotti P et al (2002) Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells. Am J Pathol 160:673–680PubMedGoogle Scholar
  57. 57.
    Sidhu SS, Mengistab AT, Tauscher AN, LaVail J, Basbaum C (2004) The microvesicle as a vehicle for EMMPRIN in tumor-stromal interactions. Oncogene 23:956–963PubMedGoogle Scholar
  58. 58.
    Brill A, Dashevsky O, Rivo J, Gozal Y, Varon D (2005) Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovasc Res 67:30–38PubMedGoogle Scholar
  59. 59.
    Gesierich S, Berezovskiy I, Ryschich E, Zoller M (2006) Systemic induction of the angiogenesis switch by the tetraspanin D6.1A/CO-029. Cancer Res 66:7083–7094PubMedGoogle Scholar
  60. 60.
    Deregibus MC, Cantaluppi V, Calogero R et al (2007) Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 110:2440–2448PubMedGoogle Scholar
  61. 61.
    Al-Nedawi K, Meehan B, Micallef J et al (2008) Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 10:619–624PubMedGoogle Scholar
  62. 62.
    Greco V, Hannus M, Eaton S (2001) Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell 106:633–645PubMedGoogle Scholar
  63. 63.
    Martinez MC, Larbret F, Zobairi F et al (2006) Transfer of differentiation signal by membrane microvesicles harboring hedgehog morphogens. Blood 108:3012–3020PubMedGoogle Scholar
  64. 64.
    Conde-Vancells J, Gonzalez E, Lu SC, Mato JM, Falcon-Perez JM (2010) Overview of extracellular microvesicles in drug metabolism. Expert Opin Drug Metab Toxicol 6:543–554PubMedGoogle Scholar
  65. 65.
    Landsverk T, Trevella W, Nicander L (1990) Transfer of carbonic anhydrase-positive particles from the follicle-associated epithelium to lymphocytes of Peyer's patches in foetal sheep and lambs. Cell Tissue Res 261:239–247PubMedGoogle Scholar
  66. 66.
    Dolo V, D'Ascenzo S, Giusti I et al (2005) Shedding of membrane vesicles by tumor and endothelial cells. Ital J Anat Embryol 110:127–133PubMedGoogle Scholar
  67. 67.
    Sarkar A, Mitra S, Mehta S, Raices R, Wewers MD (2009) Monocyte derived microvesicles deliver a cell death message via encapsulated caspase-1. PLoS ONE 4:e7140PubMedGoogle Scholar
  68. 68.
    Zwicker JI, Liebman HA, Neuberg D et al (2009) Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy. Clin Cancer Res 15:6830–6840PubMedGoogle Scholar
  69. 69.
    Sustar V, Jansa R, Frank M et al (2009) Suppression of membrane microvesiculation—a possible anticoagulant and anti-tumor progression effect of heparin. Blood Cells Mol Dis 42:223–227PubMedGoogle Scholar
  70. 70.
    Valadi H, Ekstrom K, Bossios A et al (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659PubMedGoogle Scholar
  71. 71.
    Ratajczak J, Miekus K, Kucia M et al (2006) Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20:847–856PubMedGoogle Scholar
  72. 72.
    Skog J, Wurdinger T, van Rijn S et al (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10:1470–1476PubMedGoogle Scholar
  73. 73.
    Yuan A, Farber EL, Rapoport AL et al (2009) Transfer of microRNAs by embryonic stem cell microvesicles. PLoS ONE 4:e4722PubMedGoogle Scholar
  74. 74.
    Watanabe J, Marathe GK, Neilsen PO et al (2003) Endotoxins stimulate neutrophil adhesion followed by synthesis and release of platelet-activating factor in microparticles. J Biol Chem 278:33161–33168PubMedGoogle Scholar
  75. 75.
    Liu R, Klich I, Ratajczak J, Ratajczak MZ, Zuba-Surma EK (2009) Erythrocyte-derived microvesicles may transfer phosphatidylserine to the surface of nucleated cells and falsely ‘mark’ them as apoptotic. Eur J Haematol 83:220–229PubMedGoogle Scholar
  76. 76.
    Lespagnol A, Duflaut D, Beekman C 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 15:1723–1733PubMedGoogle Scholar
  77. 77.
    Muralidharan-Chari V, Clancy J, Plou C et al (2009) ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol 19:1875–1885PubMedGoogle Scholar
  78. 78.
    D'Asti E, and Rak J (2010) Unpublished observation. Data fileGoogle Scholar
  79. 79.
    Guescini M, Genedani S, Stocchi V, Agnati LF (2010) Astrocytes and glioblastoma cells release exosomes carrying mtDNA. J Neural Transm 117:1–4PubMedGoogle Scholar
  80. 80.
    Heijnen HF, Schiel AE, Fijnheer R, Geuze HJ, Sixma JJ (1999) Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood 94:3791–3799PubMedGoogle Scholar
  81. 81.
    Nazarenko I, Rana S, Baumann A et al (2010) Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation. Cancer Res 70:1668–1678PubMedGoogle Scholar
  82. 82.
    Baran J, Baj-Krzyworzeka M, Weglarczyk K et al (2010) Circulating tumour-derived microvesicles in plasma of gastric cancer patients. Cancer Immunol Immunother 59:841–850PubMedGoogle Scholar
  83. 83.
    Hawari FI, Rouhani FN, Cui X et al (2004) Release of full-length 55-kDa TNF receptor 1 in exosome-like vesicles: a mechanism for generation of soluble cytokine receptors. Proc Natl Acad Sci USA 101:1297–1302PubMedGoogle Scholar
  84. 84.
    Kim CW, Lee HM, Lee TH et al (2002) Extracellular membrane vesicles from tumor cells promote angiogenesis via sphingomyelin. Cancer Res 62:6312–6317PubMedGoogle Scholar
  85. 85.
    Pisetsky DS, Gauley J, Ullal AJ (2010) Microparticles as a source of extracellular DNA. Immunol Res. doi: 10.1007/s12026-010-8184-8
  86. 86.
    Heppner GH (1989) Tumor cell societies. J Natl Cancer Inst 81:648–649PubMedGoogle Scholar
  87. 87.
    Yu J, May L, Milsom C et al (2008) Contribution of host-derived tissue factor to tumor neovascularization. Arterioscler Thromb Vasc Biol 28:1975–1981PubMedGoogle Scholar
  88. 88.
    Schiera G, Proia P, Alberti C et al (2007) Neurons produce FGF2 and VEGF and secrete them at least in part by shedding extracellular vesicles. J Cell Mol Med 11:1384–1394PubMedGoogle Scholar
  89. 89.
    Ostrowski M, Carmo NB, Krumeich S et al (2010) Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 12:19–30PubMedGoogle Scholar
  90. 90.
    Zoller M (2009) Tetraspanins: push and pull in suppressing and promoting metastasis. Nat Rev Cancer 9:40–55PubMedGoogle Scholar
  91. 91.
    Bravo-Cordero JJ, Marrero-Diaz R, Megias D et al (2007) MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway. EMBO J 26:1499–1510PubMedGoogle Scholar
  92. 92.
    Dvorak HF, Quay SC, Orenstein NS et al (1981) Tumor shedding and coagulation. Science 212:923–924PubMedGoogle Scholar
  93. 93.
    Jung T, Castellana D, Klingbeil P et al (2009) CD44v6 dependence of premetastatic niche preparation by exosomes. Neoplasia 11:1093–1105PubMedGoogle Scholar
  94. 94.
    Amzallag N, Passer BJ, Allanic D et al (2004) TSAP6 facilitates the secretion of translationally controlled tumor protein/histamine-releasing factor via a nonclassical pathway. J Biol Chem 279:46104–46112PubMedGoogle Scholar
  95. 95.
    Cocucci E, Racchetti G, Meldolesi J (2009) Shedding microvesicles: artefacts no more. Trends Cell Biol 19:43–51PubMedGoogle Scholar
  96. 96.
    Huber V, Fais S, Iero M et al (2005) Human colorectal cancer cells induce T-cell death through release of proapoptotic microvesicles: role in immune escape. Gastroenterology 128:1796–1804PubMedGoogle Scholar
  97. 97.
    Koga K, Matsumoto K, Akiyoshi T et al (2005) Purification, characterization and biological significance of tumor-derived exosomes. Anticancer Res 25:3703–3707PubMedGoogle Scholar
  98. 98.
    Giesen PL, Rauch U, Bohrmann B et al (1999) Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci USA 96:2311–2315PubMedGoogle Scholar
  99. 99.
    Castellana D, Toti F, Freyssinet JM (2010) Membrane microvesicles: Macromessengers in cancer disease and progression. Thromb Res 125:S84–S88PubMedGoogle Scholar
  100. 100.
    Milsom CC, Yu JL, Mackman N et al (2008) Tissue factor regulation by epidermal growth factor receptor and epithelial-to-mesenchymal transitions: effect on tumor initiation and angiogenesis. Cancer Res 68:10068–10076PubMedGoogle Scholar
  101. 101.
    Janowska-Wieczorek A, Wysoczynski M, Kijowski J et al (2005) Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer 113:752–760PubMedGoogle Scholar
  102. 102.
    Leroyer AS, Rautou PE, Silvestre JS et al (2008) CD40 ligand+ microparticles from human atherosclerotic plaques stimulate endothelial proliferation and angiogenesis a potential mechanism for intraplaque neovascularization. J Am Coll Cardiol 52:1302–1311PubMedGoogle Scholar
  103. 103.
    Parolini I, Federici C, Raggi C et al (2009) Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem 284:34211–34222PubMedGoogle Scholar
  104. 104.
    Park D, Tosello-Trampont AC, Elliott MR et al (2007) BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450:430–434PubMedGoogle Scholar
  105. 105.
    Rozmyslowicz T, Majka M, Kijowski J et al (2003) Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV. AIDS 17:33–42PubMedGoogle Scholar
  106. 106.
    Salanova B, Choi M, Rolle S et al (2007) Beta2-integrins and acquired glycoprotein IIb/IIIa (GPIIb/IIIa) receptors cooperate in NF-kappaB activation of human neutrophils. J Biol Chem 282:27960–27969PubMedGoogle Scholar
  107. 107.
    Prokopi M, Pula G, Mayr U et al (2009) Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures. Blood 114:723–732PubMedGoogle Scholar
  108. 108.
    Obregon C, Rothen-Rutishauser B, Gerber P, Gehr P, Nicod LP (2009) Active uptake of dendritic cell-derived exovesicles by epithelial cells induces the release of inflammatory mediators through a TNF-alpha-mediated pathway. Am J Pathol 175:696–705PubMedGoogle Scholar
  109. 109.
    Deregibus MC, Tetta C, Camussi G (2010) The dynamic stem cell microenvironment is orchestrated by microvesicle-mediated transfer of genetic information. Histol Histopathol 25:397–404PubMedGoogle Scholar
  110. 110.
    Janowska-Wieczorek A, Marquez-Curtis LA, Wysoczynski M, Ratajczak MZ (2006) Enhancing effect of platelet-derived microvesicles on the invasive potential of breast cancer cells. Transfusion 46:1199–1209PubMedGoogle Scholar
  111. 111.
    Aharon A, Brenner B (2009) Microparticles, thrombosis and cancer. Best Pract Res Clin Haematol 22:61–69PubMedGoogle Scholar
  112. 112.
    Perez-Casal M, Downey C, Cutillas-Moreno B et al (2009) Microparticle-associated endothelial protein C receptor and the induction of cytoprotective and anti-inflammatory effects. Haematologica 94:387–394PubMedGoogle Scholar
  113. 113.
    Collino F, Deregibus MC, Bruno S et al (2010) Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS ONE 5:e11803PubMedGoogle Scholar
  114. 114.
    Barry OP, Kazanietz MG, Pratico D, FitzGerald GA (1999) Arachidonic acid in platelet microparticles up-regulates cyclooxygenase-2-dependent prostaglandin formation via a protein kinase C/mitogen-activated protein kinase-dependent pathway. J Biol Chem 274:7545–7556PubMedGoogle Scholar
  115. 115.
    Yu JL, May L, Lhotak V et al (2005) Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis. Blood 105:1734–1741PubMedGoogle Scholar
  116. 116.
    Di Vizio D, Kim J, Hager MH et al (2009) Oncosome formation in prostate cancer: association with a region of frequent chromosomal deletion in metastatic disease. Cancer Res 69:5601–5609PubMedGoogle Scholar
  117. 117.
    Slaughter DP, Southwick HW, Smejkal W (1953) Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 6:963–968PubMedGoogle Scholar
  118. 118.
    Taylor DD, Gercel-Taylor C (2008) MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 110:13–21PubMedGoogle Scholar
  119. 119.
    Li J, Sherman-Baust CA, Tsai-Turton M et al (2009) Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer. BMC Cancer 9:244PubMedGoogle Scholar
  120. 120.
    Milsom C, Yu J, May L et al (2007) The role of tumor-and host-related tissue factor pools in oncogene-driven tumor progression. Thromb Res 120(Suppl 2):S82–S91PubMedGoogle Scholar
  121. 121.
    Thomas GM, Panicot-Dubois L, Lacroix R et al (2009) Cancer cell-derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo. J Exp Med 206:1913–1927PubMedGoogle Scholar
  122. 122.
    Angelucci A, D'Ascenzo S, Festuccia C (2000) Vesicle-associated urokinase plasminogen activator promotes invasion in prostate cancer cell lines. Clin Exp Metastasis 18:163–170PubMedGoogle Scholar
  123. 123.
    Gastpar R, Gehrmann M, Bausero MA et al (2005) Heat shock protein 70 surfacepositive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res 65:5238–5247PubMedGoogle Scholar
  124. 124.
    Hong BS, Cho JH, Kim H et al (2009) Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells. BMC Genomics 10:556PubMedGoogle Scholar
  125. 125.
    Calzolari A, Raggi C, Deaglio S et al (2006) TfR2 localizes in lipid raft domains and is released in exosomes to activate signal transduction along the MAPK pathway. J Cell Sci 119:4486–4498PubMedGoogle Scholar
  126. 126.
    Logozzi M, De MA, Lugini L et al (2009) High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients. PLoS ONE 4:e5219PubMedGoogle Scholar
  127. 127.
    Pisitkun T, Shen RF, Knepper MA (2004) Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci USA 101:13368–13373PubMedGoogle Scholar
  128. 128.
    Hsu C, Morohashi Y, Yoshimura S et al (2010) Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C. J Cell Biol 189:223–232PubMedGoogle Scholar
  129. 129.
    Mallegol J, Van NG, Lebreton C et al (2007) T84-intestinal epithelial exosomes bear MHC class II/peptide complexes potentiating antigen presentation by dendritic cells. Gastroenterology 132:1866–1876PubMedGoogle Scholar
  130. 130.
    Jy W, Horstman LL, Jimenez JJ et al (2004) Measuring circulating cell-derived microparticles. J Thromb Haemost 2:1842–1851PubMedGoogle Scholar
  131. 131.
  132. 132.
    Diamant M, Tushuizen ME, Sturk A, Nieuwland R (2004) Cellular microparticles: new players in the field of vascular disease? Eur J Clin Investig 34:392–401Google Scholar
  133. 133.
    Mrvar-Brecko A, Sustar V, Jansa V et al (2010) Isolated microvesicles from peripheral blood and body fluids as observed by scanning electron microscope. Blood Cells Mol Dis 44:307–312PubMedGoogle Scholar
  134. 134.
    Kang D, Oh S, Ahn SM, Lee BH, Moon MH (2008) Proteomic analysis of exosomes from human neural stem cells by flow field-flow fractionation and nanoflow liquid chromatography-tandem mass spectrometry. J Proteome Res 7:3475–3480PubMedGoogle Scholar
  135. 135.
  136. 136.
    Sanderson MP, Keller S, Alonso A et al (2008) Generation of novel, secreted epidermal growth factor receptor (EGFR/ErbB1) isoforms via metalloprotease-dependent ectodomain shedding and exosome secretion. J Cell Biochem 103:1783–1797PubMedGoogle Scholar
  137. 137.
    Andreola G, Rivoltini L, Castelli C et al (2002) Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. J Exp Med 195:1303–1316PubMedGoogle Scholar
  138. 138.
    Thery C, Clayton A, Amigorena S, Raposo G (2006) Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Current Protocols in Cell Biology. John Wiley & Sons Inc. 3.22.1–3.22.29Google Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Tae Hoon Lee
    • 1
  • Esterina D’Asti
    • 1
  • Nathalie Magnus
    • 1
  • Khalid Al-Nedawi
    • 1
  • Brian Meehan
    • 1
  • Janusz Rak
    • 1
  1. 1.Montreal Children’s Hospital Research InstituteMcGill UniversityMontrealCanada

Personalised recommendations