Microvesicles as mediators of intercellular communication in cancer—the emerging science of cellular ‘debris’
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Citri A, Yarden Y (2006) EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol 7:505–516
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 20:1487–1495
Sherer NM, Mothes W (2008) Cytonemes and tunneling nanotubules in cell-cell communication and viral pathogenesis. Trends Cell Biol 18:414–420
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
Thery C, Ostrowski M, Segura E (2009) Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9:581–593
Mathivanan S, Ji H, Simpson RJ (2010) Exosomes: extracellular organelles important in intercellular communication. J Proteomics 73:1907–1920
Caumartin J, Lemaoult J, Carosella ED (2006) Intercellular exchanges of membrane patches (trogocytosis) highlight the next level of immune plasticity. Transpl Immunol 17:20–22
Simons M, Raposo G (2009) Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol 21:575–581
Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L (2010) Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int 78:838–848
Muralidharan-Chari V, Clancy JW, Sedgwick A, Souza-Schorey C (2010) Microvesicles: mediators of extracellular communication during cancer progression. J Cell Sci 123:1603–1611
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 27:375–387
Mause SF, Weber C (2010) Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res 107:1047–1057
Trams EG, Lauter CJ, Salem N Jr, Heine U (1981) Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta 645:63–70
Vindelov LL, Christensen IJ, Keiding N, Spang-Thomsen M, Nissen NI (1983) Long-term storage of samples for flow cytometric DNA analysis. Cytometry 3:317–322
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
Al-Nedawi K, Meehan B, Rak J (2009) Microvesicles: messengers and mediators of tumor progression. Cell Cycle 8:2014–2018
Bergsmedh A, Szeles A, Henriksson M et al (2001) Horizontal transfer of oncogenes by uptake of apoptotic bodies. Proc Natl Acad Sci USA 98:6407–6411
Wolf P (1967) The nature and significance of platelet products in human plasma. Br J Haematol 13:269–288
Lee T-H, Rak J (2011) Unpublished observation. Data file
Simpson RJ, Lim JW, Moritz RL, Mathivanan S (2009) Exosomes: proteomic insights and diagnostic potential. Expert Rev Proteomics 6:267–283
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 118:2849–2858
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):17615–17622
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 106:1604–1611
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
Irion U, St JD (2007) bicoid RNA localization requires specific binding of an endosomal sorting complex. Nature 445:554–558
Lozano J, Morales A, Cremesti A et al (2001) Niemann-Pick disease versus acid sphingomyelinase deficiency. Cell Death Differ 8:100–103
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 99:4030–4038
Piccin A, Murphy WG, Smith OP (2007) Circulating microparticles: pathophysiology and clinical implications. Blood Rev 21:157–171
Burnier L, Fontana P, Kwak BR, Ngelillo-Scherrer A (2009) Cell-derived microparticles in haemostasis and vascular medicine. Thromb Haemost 101:439–451
Bianco F, Perrotta C, Novellino L et al (2009) Acid sphingomyelinase activity triggers microparticle release from glial cells. EMBO J 28:1043–1054
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 99:86–95
Millimaggi D, Mari M, D'Ascenzo S et al (2007) Tumor vesicle-associated CD147 modulates the angiogenic capability of endothelial cells. Neoplasia 9:349–357
Yu X, Harris SL, Levine AJ (2006) The regulation of exosome secretion: a novel function of the p53 protein. Cancer Res 66:4795–4801
Williams RL, Urbe S (2007) The emerging shape of the ESCRT machinery. Nat Rev Mol Cell Biol 8:355–368
Trajkovic K, Hsu C, Chiantia S et al (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319:1244–1247
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 106:3794–3799
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:S163
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 101:942–948
Johnstone RM (2006) Exosomes biological significance: a concise review. Blood Cells Mol Dis 36:315–321
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):1079–1091
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 115:1755–1764
Bebawy M, Combes V, Lee E et al (2009) Membrane microparticles mediate transfer of P-glycoprotein to drug sensitive cancer cells. Leukemia 23:1643–1649
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 116:2385–2394
Hendrix A, Westbroek W, Bracke M, De WO (2010) An ex(o)citing machinery for invasive tumor growth. Cancer Res 70:9533–9537
Zwicker JI (2010) Predictive value of tissue factor bearing microparticles in cancer associated thrombosis. Thromb Res 125:S89–S91
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 91:3862–3874
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 8:96–103
Zhou Z (2007) New phosphatidylserine receptors: clearance of apoptotic cells and more. Dev Cell 13:759–760
Celi A, Lorenzet R, Furie BC, Furie B (2004) Microparticles and a P-selectin-mediated pathway of blood coagulation. Dis Markers 20:347–352
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 5:520–527
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 6:769–775
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 25:1512–1518
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, Montreal
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 160:673–680
Sidhu SS, Mengistab AT, Tauscher AN, LaVail J, Basbaum C (2004) The microvesicle as a vehicle for EMMPRIN in tumor-stromal interactions. Oncogene 23:956–963
Brill A, Dashevsky O, Rivo J, Gozal Y, Varon D (2005) Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovasc Res 67:30–38
Gesierich S, Berezovskiy I, Ryschich E, Zoller M (2006) Systemic induction of the angiogenesis switch by the tetraspanin D6.1A/CO-029. Cancer Res 66:7083–7094
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 110:2440–2448
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 10:619–624
Greco V, Hannus M, Eaton S (2001) Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell 106:633–645
Martinez MC, Larbret F, Zobairi F et al (2006) Transfer of differentiation signal by membrane microvesicles harboring hedgehog morphogens. Blood 108:3012–3020
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 6:543–554
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 261:239–247
Dolo V, D'Ascenzo S, Giusti I et al (2005) Shedding of membrane vesicles by tumor and endothelial cells. Ital J Anat Embryol 110:127–133
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:e7140
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 15:6830–6840
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 42:223–227
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 9:654–659
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 20:847–856
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 10:1470–1476
Yuan A, Farber EL, Rapoport AL et al (2009) Transfer of microRNAs by embryonic stem cell microvesicles. PLoS ONE 4:e4722
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 278:33161–33168
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 83:220–229
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 15:1723–1733
Muralidharan-Chari V, Clancy J, Plou C et al (2009) ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol 19:1875–1885
D'Asti E, and Rak J (2010) Unpublished observation. Data file
Guescini M, Genedani S, Stocchi V, Agnati LF (2010) Astrocytes and glioblastoma cells release exosomes carrying mtDNA. J Neural Transm 117:1–4
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 94:3791–3799
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 70:1668–1678
Baran J, Baj-Krzyworzeka M, Weglarczyk K et al (2010) Circulating tumour-derived microvesicles in plasma of gastric cancer patients. Cancer Immunol Immunother 59:841–850
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 101:1297–1302
Kim CW, Lee HM, Lee TH et al (2002) Extracellular membrane vesicles from tumor cells promote angiogenesis via sphingomyelin. Cancer Res 62:6312–6317
Pisetsky DS, Gauley J, Ullal AJ (2010) Microparticles as a source of extracellular DNA. Immunol Res. doi: 10.1007/s12026-010-8184-8
Yu J, May L, Milsom C et al (2008) Contribution of host-derived tissue factor to tumor neovascularization. Arterioscler Thromb Vasc Biol 28:1975–1981
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 11:1384–1394
Ostrowski M, Carmo NB, Krumeich S et al (2010) Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 12:19–30
Zoller M (2009) Tetraspanins: push and pull in suppressing and promoting metastasis. Nat Rev Cancer 9:40–55
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 26:1499–1510
Jung T, Castellana D, Klingbeil P et al (2009) CD44v6 dependence of premetastatic niche preparation by exosomes. Neoplasia 11:1093–1105
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 279:46104–46112
Cocucci E, Racchetti G, Meldolesi J (2009) Shedding microvesicles: artefacts no more. Trends Cell Biol 19:43–51
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 128:1796–1804
Koga K, Matsumoto K, Akiyoshi T et al (2005) Purification, characterization and biological significance of tumor-derived exosomes. Anticancer Res 25:3703–3707
Giesen PL, Rauch U, Bohrmann B et al (1999) Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci USA 96:2311–2315
Castellana D, Toti F, Freyssinet JM (2010) Membrane microvesicles: Macromessengers in cancer disease and progression. Thromb Res 125:S84–S88
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 68:10068–10076
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 113:752–760
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 52:1302–1311
Parolini I, Federici C, Raggi C et al (2009) Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem 284:34211–34222
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 450:430–434
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 17:33–42
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 282:27960–27969
Prokopi M, Pula G, Mayr U et al (2009) Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures. Blood 114:723–732
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 175:696–705
Deregibus MC, Tetta C, Camussi G (2010) The dynamic stem cell microenvironment is orchestrated by microvesicle-mediated transfer of genetic information. Histol Histopathol 25:397–404
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 46:1199–1209
Aharon A, Brenner B (2009) Microparticles, thrombosis and cancer. Best Pract Res Clin Haematol 22:61–69
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 94:387–394
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:e11803
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 274:7545–7556
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 105:1734–1741
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 69:5601–5609
Slaughter DP, Southwick HW, Smejkal W (1953) Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 6:963–968
Taylor DD, Gercel-Taylor C (2008) MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 110:13–21
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 9:244
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–S91
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 206:1913–1927
Angelucci A, D'Ascenzo S, Festuccia C (2000) Vesicle-associated urokinase plasminogen activator promotes invasion in prostate cancer cell lines. Clin Exp Metastasis 18:163–170
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 65:5238–5247
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 10:556
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 119:4486–4498
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:e5219
Pisitkun T, Shen RF, Knepper MA (2004) Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci USA 101:13368–13373
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 189:223–232
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 132:1866–1876
Jy W, Horstman LL, Jimenez JJ et al (2004) Measuring circulating cell-derived microparticles. J Thromb Haemost 2:1842–1851
www.biooscientific.com . 2010
Diamant M, Tushuizen ME, Sturk A, Nieuwland R (2004) Cellular microparticles: new players in the field of vascular disease? Eur J Clin Investig 34:392–401
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 44:307–312
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 7:3475–3480
www.nanosight.com/products/lm10 . 2010
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 103:1783–1797
Andreola G, Rivoltini L, Castelli C et al (2002) Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. J Exp Med 195:1303–1316