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Extracellular vesicles such as prostate cancer cell fragments as a fluid biopsy for prostate cancer

Abstract

Extracellular vesicles (EVs) are cell-derived vesicles generated through a process of cell membrane shedding or storage vesicle release, as occurs during apoptosis, necrosis or exocytosis. Initially perceived as cellular by-products or ‘dust’ of insignificant biological importance, recent research has shed light on the role of EVs as mediators of intercellular communication, blood coagulation and disease progression. The prostate is a source of EVs and their abundance in complex biological fluids such as plasma, serum and urine make them compelling entities for a ‘fluid biopsy’. As such, prostate cancer cell fragments (PCCF) are EVs generated by the tumor resident within the prostate and are also present in blood, expressing a portion of biomarkers representative of the primary tumor. High-throughput analytical techniques to determine biomarker expression on EVs is the last hurdle towards translating the full potential of prostate EVs for clinical use. We describe current state-of-the-art methods for the analysis of prostate-derived EVs in patient fluids such as plasma and the challenges that lie ahead in this emerging field of translational research.

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References

  1. Lee TH, D’Asti E, Magnus N, Al-Nedawi K, Meehan B, Rak J . Microvesicles as mediators of intercellular communication in cancer-the emerging science of cellular ‘debris’. Semin Immunopathol 2011; 33: 455–467.

    Article  PubMed  Google Scholar 

  2. Wang W, Li H, Zhou Y, Jie S . Peripheral blood microvesicles are potential biomarkers for hepatocellular carcinoma. Cancer Biomark 2013; 13: 351–357.

    Article  CAS  PubMed  Google Scholar 

  3. Sahlén GE, Egevad L, Ahlander A, Norlén BJ, Ronquist G, Nilsson BO . Ultrastructure of the secretion of prostasomes from benign and malignant epithelial cells in the prostate. Prostate 2002; 53: 192–199.

    Article  PubMed  Google Scholar 

  4. Duijvesz D, Burnum-Johnson KE, Gritsenko MA, Hoogland AM, Vredenbregt-van den Berg MS, Willemsen R et al. Proteomic profiling of exosomes leads to the identification of novel biomarkers for prostate cancer. PLoS One 2013; 8: e82589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Théry C, Zitvogel L, Amigorena S . Exosomes: composition, biogenesis and function. Nat Rev Immunol 2002; 2: 569–579.

    Article  CAS  PubMed  Google Scholar 

  6. Berda-Haddad Y, Robert S, Salers P, Zekraoui L, Farnarier C, Dinarello CA et al. Sterile inflammation of endothelial cell-derived apoptotic bodies is mediated by interleukin-1α. Proc Natl Acad Sci USA 2011; 108: 20684–20689.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. George JN, Thoi LL, McManus LM, Reimann TA . Isolation of human platelet membrane microparticles from plasma and serum. Blood 1982; 60: 834–840.

    CAS  PubMed  Google Scholar 

  8. Leong HS, Mahesh BM, Day JR, Smith JD, McCormack AD, Ghimire G et al. Vimentin autoantibodies induce platelet activation and formation of platelet-leukocyte conjugates via platelet-activating factor. J Leukoc Biol 2008; 83: 263–271.

    Article  CAS  PubMed  Google Scholar 

  9. Al-Nedawi K, Meehan B, Rak J . Microvesicles: messengers and mediators of tumor progression. Cell Cycle 2009; 8: 2014–2018.

    Article  CAS  PubMed  Google Scholar 

  10. Martínez MC, Tesse A, Zobairi F, Andriantsitohaina R . Shed membrane microparticles from circulating and vascular cells in regulating vascular function. Am J Physiol Heart Circ Physiol 2005; 288: H1004–H1009.

    Article  CAS  PubMed  Google Scholar 

  11. Ronquist G, Hedström M . Restoration of detergent-inactivated adenosine triphosphatase activity of human prostatic fluid with concanavalin A. Biochim Biophys Acta 1977; 483: 483–486.

    Article  CAS  PubMed  Google Scholar 

  12. Brody I, Ronquist G, Gottfries A . Ultrastructural localization of the prostasome - an organelle in human seminal plasma. Ups J Med Sci 1983; 88: 63–80.

    Article  CAS  PubMed  Google Scholar 

  13. Sahlén G, Ahlander A, Frost A, Ronquist G, Norlén BJ, Nilsson BO . Prostasomes are secreted from poorly differentiated cells of prostate cancer metastases. Prostate 2004; 61: 291–297.

    Article  PubMed  Google Scholar 

  14. Drake RR, Kislinger T . The proteomics of prostate cancer exosomes. Expert Rev Proteomics 2014; 11: 167–177.

    Article  CAS  PubMed  Google Scholar 

  15. Tarazona R, Delgado E, Guarnizo MC, Roncero RG, Morgado S, Sánchez-Correa B et al. Human prostasomes express CD48 and interfere with NK cell function. Immunobiology 2011; 216: 41–46.

    Article  CAS  PubMed  Google Scholar 

  16. Nilsson BO, Carlsson L, Larsson A, Ronquist G . Autoantibodies to prostasomes as new markers for prostate cancer. Ups J Med Sci 2001; 106: 43–49.

    Article  CAS  PubMed  Google Scholar 

  17. Tavoosidana G, Ronquist G, Darmanis S, Yan J, Carlsson L, Wu D et al. Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer. Proc Natl Acad Sci USA 2011; 108: 8809–8814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sardana G, Diamandis EP . Biomarkers for the diagnosis of new and recurrent prostate cancer. Biomark Med 2012; 6: 587–596.

    Article  CAS  PubMed  Google Scholar 

  19. Jansen FH, Krijgsveld J, van Rijswijk A, van den Bemd G-J, van den Berg MS, van Weerden WM et al. Exosomal secretion of cytoplasmic prostate cancer xenograft-derived proteins. Mol Cell Proteomics 2009; 8: 1192–1205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Liu T, Mendes DE, Berkman CE . Functional prostate-specific membrane antigen is enriched in exosomes from prostate cancer cells. Int J Oncol 2014; 44: 918–922.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ronquist GK, Larsson A, Stavreus-Evers A, Ronquist G . Prostasomes are heterogeneous regarding size and appearance but affiliated to one DNA-containing exosome family. Prostate 2012; 72: 1736–1745.

    Article  CAS  PubMed  Google Scholar 

  22. Ihlaseh-Catalano SM, Drigo SA, de Jesus CM, Domingues MA, Trindade Filho JC, de Camargo JL et al. STEAP1 protein overexpression is an independent marker for biochemical recurrence in prostate carcinoma. Histopathology 2013; 63: 678–685.

    PubMed  Google Scholar 

  23. Porkka KP, Helenius MA, Visakorpi T . Cloning and characterization of a novel six- transmembrane protein STEAP2, expressed in normal and malignant prostate. Lab Invest 2002; 82: 1573–1582.

    Article  CAS  PubMed  Google Scholar 

  24. Zhigang Z, Wenlv S . Prostate stem cell antigen (PSCA) expression in human prostate cancer tissues and its potential role in prostate carcinogenesis and progression of prostate cancer. World J Surg Oncol 2004; 2: 13.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Di Vizio D, Morello M, Dudley AC, Schow PW, Adam RM, Morley S et al. Large oncosomes in human prostate cancer tissues and in the circulation of mice with metastatic disease. Am J Pathol 2012; 181: 1573–1584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chambers AF, Groom AC, MacDonald IC . Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2002; 2: 563–572.

    Article  CAS  PubMed  Google Scholar 

  27. Ligthart ST, Coumans FAW, Attard G, Cassidy AM, de Bono JS, Terstappen LW . Unbiased and automated identification of a circulating tumour cell definition that associates with overall survival. PLoS One 2011; 6: e27419.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Goodman OB, Symanowski JT, Loudyi A, Fink LM, Ward DC, Vogelzang NJ . Circulating tumor cells as a predictive biomarker in patients with hormone-sensitive prostate cancer. Clin Genitourin Cancer 2011; 9: 31–38.

    Article  PubMed  Google Scholar 

  29. Adams DL, Stefansson S, Haudenschild C, Martin SS, Charpentier M, Chumsri S et al. Cytometric characterization of circulating tumor cells captured by microfiltration and their correlation to the CellSearch(®) CTC test. Cytometry A 2014; 87: 137–144.

    Article  CAS  PubMed  Google Scholar 

  30. Lowes LE, Lock M, Rodrigues G, D’Souza D, Bauman G, Ahmad B et al. Circulating tumour cells in prostate cancer patients receiving salvage radiotherapy. Clin Transl Oncol 2012; 14: 150–156.

    Article  CAS  PubMed  Google Scholar 

  31. Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 2004; 351: 781–791.

    Article  CAS  PubMed  Google Scholar 

  32. Coumans FA, Doggen CJ, Attard G, de Bono JS, Terstappen LW . All circulating EpCAM+CK+CD45- objects predict overall survival in castration-resistant prostate cancer. Ann Oncol 2010; 21: 1851–1857.

    Article  CAS  PubMed  Google Scholar 

  33. Khan S, Jutzy JM, Valenzuela MM, Turay D, Aspe JR, Ashok A et al. Plasma- derived exosomal survivin, a plausible biomarker for early detection of prostate cancer. PLoS One 2012; 7: e46737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. De Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 2008; 14: 6302–6309.

    Article  CAS  PubMed  Google Scholar 

  35. Klein EA, Cooperberg MR, Magi-Galluzzi C, Simko JP, Falzarano SM, Maddala T et al. A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur Urol 2014; 66: 550–560.

    Article  PubMed  Google Scholar 

  36. Corcoran C, Rani S, O’Driscoll L . miR-34a is an intracellular and exosomal predictive biomarker for response to docetaxel with clinical relevance to prostate cancer progression. Prostate 2014; 74: 1320–1334.

    Article  CAS  PubMed  Google Scholar 

  37. Mesri M, Altieri DC . Endothelial cell activation by leukocyte microparticles. J Immunol 1998; 161: 4382–4387.

    CAS  PubMed  Google Scholar 

  38. Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L, Guha A et al. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 2008; 10: 619–624.

    Article  CAS  PubMed  Google Scholar 

  39. Peinado H, Alečković M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 2012; 18: 883–891.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO . Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9: 654–659.

    Article  CAS  PubMed  Google Scholar 

  41. Hong BS, Cho J-H, Kim H, Choi E-J, Rho S, Kim J et al. Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells. BMC Genomics 2009; 10: 556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bartels CL, Tsongalis GJ . MicroRNAs: novel biomarkers for human cancer. Clin Chem 2009; 55: 623–631.

    Article  CAS  PubMed  Google Scholar 

  43. Selth LA, Townley S, Gillis JL, Ochnik AM, Murti K, Macfarlane RJ et al. Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease. Int J Cancer 2012; 131: 652–661.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  45. Rabinowits G, Gerçel-Taylor C, Day JM, Taylor DD, Kloecker GH . Exosomal microRNA: a diagnostic marker for lung cancer. Clin Lung Cancer 2009; 10: 42–46.

    Article  CAS  PubMed  Google Scholar 

  46. Melo SA, Sugimoto H, O’Connell JT, Kato N, Villanueva A, Vidal A et al. Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell 2014; 26: 707–721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Utleg AG, Yi EC, Xie T, Shannon P, White JT, Goodlett DR et al. Proteomic analysis of human prostasomes. Prostate 2003; 56: 150–161.

    Article  CAS  PubMed  Google Scholar 

  48. Leong HS, Podor TJ, Manocha B, Lewis JD . Validation of flow cytometric detection of platelet microparticles and liposomes by atomic force microscopy. J Thromb Haemost 2011; 9: 2466–2476.

    Article  CAS  PubMed  Google Scholar 

  49. Wickman G, Julian L, Olson MF . How apoptotic cells aid in the removal of their own cold dead bodies. Cell Death Differ 2012; 19: 735–742.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Parrish AB, Freel CD, Kornbluth S . Cellular mechanisms controlling caspase activation and function. Cold Spring Harbor Perspect Biol 2013; 5: pii: a008672.

    Article  CAS  Google Scholar 

  51. Taylor RC, Cullen SP, Martin SJ . Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 2008; 9: 231–241.

    Article  CAS  PubMed  Google Scholar 

  52. Ravichandran KS . Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums. Journal Exp Med 2010; 207: 1807–1817.

    Article  CAS  Google Scholar 

  53. Bergsmedh A, Szeles A, Henriksson M, Bratt A, Folkman MJ, Spetz AL et al. Horizontal transfer of oncogenes by uptake of apoptotic bodies. Proc Natl Acad Sci USA 2001; 98: 6407–6411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Xie Y, Bai O, Yuan J, Chibbar R, Slattery K, Wei Y et al. Tumor apoptotic bodies inhibit CTL responses and antitumor immunity via membrane-bound transforming growth factor-beta1 inducing CD8+ T-cell anergy and CD4+ Tr1 cell responses. Cancer Res 2009; 69: 7756–7766.

    Article  CAS  PubMed  Google Scholar 

  55. Hargett LA, Bauer NN . On the origin of microparticles: From ‘platelet dust’ to mediators of intercellular communication. Pulm Circ 2013; 3: 329–340.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Wolf P . The nature and significance of platelet products in human plasma. Br J Haematol 1967; 13: 269–288.

    Article  CAS  PubMed  Google Scholar 

  57. Crawford N . The presence of contractile proteins in platelet microparticles isolated from human and animal platelet-free plasma. Br J Haematol 1971; 21: 53–69.

    Article  CAS  PubMed  Google Scholar 

  58. Trams EG, Lauter CJ, Salem N, Heine U . Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta 1981; 645: 63–70.

    Article  CAS  PubMed  Google Scholar 

  59. Heijnen HF, Schiel AE, Fijnheer R, Geuze HJ, Sixma JJ . Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood 1999; 94: 3791–3799.

    CAS  PubMed  Google Scholar 

  60. Wang C-C, Tseng C-C, Hsiao C-C, Chang H-C, Chang L-T, Fang W-F et al. Circulating endothelial-derived activated microparticle: a useful biomarker for predicting one-year mortality in patients with advanced non-small cell lung cancer. Biomed Res Int 2014; 2014: 173401.

    PubMed  PubMed Central  Google Scholar 

  61. Mesri M, Altieri DC . Leukocyte microparticles stimulate endothelial cell cytokine release and tissue factor induction in a JNK1 signaling pathway. J Biol Chem 1999; 274: 23111–23118.

    Article  CAS  PubMed  Google Scholar 

  62. Podor TJ, Singh D, Chindemi P, Foulon DM, McKelvie R, Weitz JI et al. Vimentin exposed on activated platelets and platelet microparticles localizes vitronectin and plasminogen activator inhibitor complexes on their surface. J Biol Chem 2002; 277: 7529–7539.

    Article  CAS  PubMed  Google Scholar 

  63. Dashevsky O, Varon D, Brill A . Platelet-derived microparticles promote invasiveness of prostate cancer cells via upregulation of MMP-2 production. Int J Cancer 2009; 124: 1773–1777.

    Article  CAS  PubMed  Google Scholar 

  64. Chironi G, Simon A, Hugel B, Del Pino M, Gariepy J, Freyssinet J-M et al. Circulating leukocyte-derived microparticles predict subclinical atherosclerosis burden in asymptomatic subjects. Arterioscler Thromb Vasc Biol 2006; 26: 2775–2780.

    Article  CAS  PubMed  Google Scholar 

  65. Combes V, Simon AC, Grau GE, Arnoux D, Camoin L, Sabatier F et al. In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. J Clin Invest 1999; 104: 93–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Tseng C-C, Wang C-C, Chang H-C, Tsai T-H, Chang L-T, Huang K-T et al. Levels of circulating microparticles in lung cancer patients and possible prognostic value. Dis Markers 2013; 35: 301–310.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008; 105: 10513–10518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Mrvar-Brecko A, Sustar V, Jansa V, Stukelj R, Jansa R, Mujagić E et al. Isolated microvesicles from peripheral blood and body fluids as observed by scanning electron microscope. Blood Cells Mol Dis 2010; 44: 307–312.

    Article  CAS  PubMed  Google Scholar 

  69. Ellis WJ, Pfitzenmaier J, Colli J, Arfman E, Lange PH, Vessella RL . Detection and isolation of prostate cancer cells from peripheral blood and bone marrow. Urology 2003; 61: 277–281.

    Article  PubMed  Google Scholar 

  70. Mizutani K, Terazawa R, Kameyama K, Kato T, Horie K, Tsuchiya T et al. Isolation of prostate cancer-related exosomes. Anticancer Res 2014; 34: 3419–3423.

    CAS  PubMed  Google Scholar 

  71. Hamilton KK, Hattori R, Esmon CT, Sims PJ . Complement proteins C5b-9 induce vesiculation of the endothelial plasma membrane and expose catalytic surface for assembly of the prothrombinase enzyme complex. J Biol Chem 1990; 265: 3809–3814.

    CAS  PubMed  Google Scholar 

  72. Chandler WL, Yeung W, Tait JF . A new microparticle size calibration standard for use in measuring smaller microparticles using a new flow cytometer. J Thromb Haemost 2011; 9: 1216–1224.

    Article  CAS  PubMed  Google Scholar 

  73. Montoro-García S, Shantsila E, Orenes-Piñero E, Lozano ML . Lip GYH. An innovative flow cytometric approach for small-size platelet microparticles: influence of calcium. Thromb Haemost 2012; 108: 373–383.

    Article  CAS  PubMed  Google Scholar 

  74. Van der Pol E, Coumans FAW, Grootemaat AE, Gardiner C, Sargent IL, Harrison P et al. Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. J Thromb Haemost 2014; 12: 1182–1192.

    Article  CAS  PubMed  Google Scholar 

  75. Hannafon BN, Ding W-Q . Intercellular communication by exosome-derived microRNAs in cancer. Int J Mol Sci 2013; 14: 14240–14269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Chevillet JR, Kang Q, Ruf IK, Briggs HA, Vojtech LN, Hughes SM et al. Quantitative and stoichiometric analysis of the microRNA content of exosomes. Proc Natl Acad Sci USA 2014; 111: 14888–14893.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Klotz L, Emberton M . Management of low risk prostate cancer-active surveillance and focal therapy. Nat Rev Clin Oncol 2014; 11: 324–334.

    Article  PubMed  Google Scholar 

  78. Abusamra AJ, Zhong Z, Zheng X, Li M, Ichim TE, Chin JL et al. Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis. Blood Cells Mol Dis 2005; 35: 169–173.

    Article  CAS  PubMed  Google Scholar 

  79. Lundholm M, Schröder M, Nagaeva O, Baranov V, Widmark A, Mincheva-Nilsson L et al. Prostate tumor-derived exosomes down-regulate NKG2D expression on natural killer cells and CD8+ T cells: mechanism of immune evasion. PLoS One 2014; 9: e108925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Bryant RJ, Pawlowski T, Catto JW, Marsden G, Vessella RL, Rhees B et al. Changes in circulating microRNA levels associated with prostate cancer. Br J Cancer 2012; 106: 768–774.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Lázaro-Ibáñez E, Sanz-Garcia A, Visakorpi T, Escobedo-Lucea C, Siljander P, Ayuso- Sacido A et al. Different gDNA content in the subpopulations of prostate cancer extracellular vesicles: apoptotic bodies, microvesicles, and exosomes. Prostate 2014; 74: 1379–1390.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Hessvik NP, Phuyal S, Brech A, Sandvig K, Llorente A . Profiling of microRNAs in exosomes released from PC-3 prostate cancer cells. Biochim Biophys Acta 2012; 1819: 1154–1163.

    Article  CAS  PubMed  Google Scholar 

  83. Inder KL, Zheng YZ, Davis MJ, Moon H, Loo D, Nguyen H et al. Expression of PTRF in PC-3 Cells modulates cholesterol dynamics and the actin cytoskeleton impacting secretion pathways. Mol Cell Proteomics 2012; 11: M111.012245.

    Article  CAS  PubMed  Google Scholar 

  84. Ronquist KG, Carlsson L, Ronquist G, Nilsson S, Larsson A . Prostasome-derived proteins capable of eliciting an immune response in prostate cancer patients. Int J Cancer 2006; 119: 847–853.

    Article  CAS  PubMed  Google Scholar 

  85. Ronquist KG, Ronquist G, Carlsson L, Larsson A . Human prostasomes contain chromosomal DNA. Prostate 2009; 69: 737–743.

    Article  CAS  PubMed  Google Scholar 

  86. Ronquist GK, Larsson A, Ronquist G, Isaksson A, Hreinsson J, Carlsson L et al. Prostasomal DNA characterization and transfer into human sperm. Mol Reprod Dev 2011; 78: 467–476.

    Article  CAS  PubMed  Google Scholar 

  87. Aberg M1, Johnell M, Wickström M, Widunder A, Siegbahn A . Simvastatin reduces the production of prothrombotic prostasomes in human prostate cancer cells. Thromb Haemost 2008; 100: 655–662.

    Article  CAS  PubMed  Google Scholar 

  88. Gomà A, Mir R, Martínez-Soler F, Tortosa A, Vidal A, Condom E et al. Multidrug resistance protein 1 localization in lipid raft domains and prostasomes in prostate cancer cell lines. Onco Targets Ther 2014; 7: 2215–2225.

    PubMed  PubMed Central  Google Scholar 

  89. Llorente A, van Deurs B, Sandvig K . Cholesterol regulates prostasome release from secretory lysosomes in PC-3 human prostate cancer cells. Eur J Cell Biol 2007; 86: 405–415.

    Article  CAS  PubMed  Google Scholar 

  90. Green TL, Santos MF, Ejaeidi AA, Craft BS, Lewis RE, Cruse JM . Toll-like receptor (TLR) expression of immune system cells from metastatic breast cancer patients with circulating tumor cells. Exp Mol Pathol 2014; 97: 44–48.

    Article  CAS  PubMed  Google Scholar 

  91. Gonzales JC, Fink LM, Goodman OB Jr, Symanowski JT, Vogelzang NJ, Ward DC . Comparison of circulating MicroRNA 141 to circulating tumor cells, lactate dehydrogenase, and prostate-specific antigen for determining treatment response in patients with metastatic prostate cancer. Clin Genitourin Cancer 2011; 9: 39–45.

    Article  PubMed  Google Scholar 

  92. Okegawa T, Itaya N, Hara H, Tambo M, Nutahara K . Circulating tumor cells as a biomarker predictive of sensitivity to docetaxel chemotherapy in patients with castration- resistant prostate cancer. Anticancer Res 2014; 34: 6705–6710.

    CAS  PubMed  Google Scholar 

  93. Doyen J, Alix-Panabières C, Hofman P, Parks SK, Chamorey E, Naman H et al. Circulating tumor cells in prostate cancer: a potential surrogate marker of survival. Crit Rev Oncol Hematol 2012; 81: 241–256.

    Article  PubMed  Google Scholar 

  94. Valenti R, Huber V, Filipazzi P, Pilla L, Sovena G, Villa A et al. Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-beta-mediated suppressive activity on T lymphocytes. Cancer Res 2006; 66: 9290–9298.

    Article  CAS  PubMed  Google Scholar 

  95. Bergmann C, Strauss L, Wang Y, Szczepanski MJ, Lang S, Johnson JT et al. T regulatory type 1 cells in squamous cell carcinoma of the head and neck: mechanisms of suppression and expansion in advanced disease. Clin Cancer Res 2008; 14: 3706–3715.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Wieckowski EU, Visus C, Szajnik M, Szczepanski MJ, Storkus WJ, Whiteside TL . Tumor-derived microvesicles promote regulatory T cell expansion and induce apoptosis in tumor-reactive activated CD8+ T lymphocytes. J Immunol 2009; 183: 3720–3730.

    Article  CAS  PubMed  Google Scholar 

  97. Sandvig K, Llorente A . Proteomic analysis of microvesicles released by the human prostate cancer cell line PC-3. Mol Cell Proteomics 2012; 11: M111.012914.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Itoh T, Ito Y, Ohtsuki Y, Ando M, Tsukamasa Y, Yamada N et al. Microvesicles released from hormone-refractory prostate cancer cells facilitate mouse pre- osteoblast differentiation. J Mol Histol 2012; 43: 509–515.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

HSL is funded by the Prostate Cancer Canada Rising Stars Grant (RS-008). SIB is funded by a Lawson Health Research IRF Studentship Grant.

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Brett, S., Kim, Y., Biggs, C. et al. Extracellular vesicles such as prostate cancer cell fragments as a fluid biopsy for prostate cancer. Prostate Cancer Prostatic Dis 18, 213–220 (2015). https://doi.org/10.1038/pcan.2015.17

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