Exosomes have been shown to act as mediators for cell to cell communication and as a potential source of biomarkers for many diseases, including prostate cancer. Exosomes are nanosized vesicles secreted by cells and consist of proteins normally found in multivesicular bodies, RNA, DNA and lipids. As a potential source of biomarkers, exosomes have attracted considerable attention, as their protein content resembles that of their cells of origin, even though it is noted that the proteins, miRNAs and lipids found in the exosomes are not a reflective stoichiometric sampling of the contents from the parent cells. While the biogenesis of exosomes in dendritic cells and platelets has been extensively characterized, much less is known about the biogenesis of exosomes in cancer cells. An understanding of the processes involved in prostate cancer will help to further elucidate the role of exosomes and other extracellular vesicles in prostate cancer progression and metastasis. There are few methodologies available for general isolation of exosomes, however validation of those methodologies is necessary to study the role of exosomal-derived biomarkers in various diseases. In this review, we discuss “exosomes” as a member of the family of extracellular vesicles and their potential to provide candidate biomarkers for prostate cancer.
References
[1]
Thery, C.; Zitvogel, L.; Amigorena, S. Exosomes: Composition, biogenesis and function. Nat. Rev. Immunol. 2002, 2, 569–579.
Akers, J.C.; Gonda, D.; Kim, R.; Carter, B.S.; Chen, C.C. Biogenesis of extracellular vesicles (EV): Exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J. Neurooncol. 2013, 113, 1–11, doi:10.1007/s11060-013-1084-8.
[4]
Thery, C.; Boussac, M.; Veron, P.; Ricciardi-Castagnoli, P.; Raposo, G.; Garin, J.; Amigorena, S. Proteomic analysis of dendritic cell-derived exosomes: A secreted subcellular compartment distinct from apoptotic vesicles. J. Immunol. 2001, 166, 7309–7318.
[5]
Valadi, H.; Ekstrom, K.; Bossios, A.; Sjostrand, M.; Lee, J.J.; Lotvall, J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 2007, 9, 654–659, doi:10.1038/ncb1596.
[6]
Ronquist, G.K.; 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, doi:10.1002/pros.22526.
[7]
Ratajczak, J.; Wysoczynski, M.; Hayek, F.; Janowska-Wieczorek, A.; Ratajczak, M.Z. Membrane-derived microvesicles: Important and underappreciated mediators of cell-to-cell communication. Leukemia 2006, 20, 1487–1495, doi:10.1038/sj.leu.2404296.
[8]
Wahlgren, J.; de Karlson, T.L.; Brisslert, M.; Vaziri Sani, F.; Telemo, E.; Sunnerhagen, P.; Valadi, H. Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res. 2012, 40, doi:10.1093/nar/gks463.
[9]
Wolfers, J.; Lozier, A.; Raposo, G.; Regnault, A.; Thery, C.; Masurier, C.; Flament, C.; Pouzieux, S.; Faure, F.; Tursz, T.; et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat. Med. 2001, 7, 297–303, doi:10.1038/85438.
[10]
Mineo, M.; Garfield, S.H.; Taverna, S.; Flugy, A.; de Leo, G.; Alessandro, R.; Kohn, E.C. Exosomes released by K562 chronic myeloid leukemia cells promote angiogenesis in a Src-dependent fashion. Angiogenesis 2012, 15, 33–45, doi:10.1007/s10456-011-9241-1.
[11]
Mathivanan, S.; Lim, J.W.; Tauro, B.J.; Ji, H.; Moritz, R.L.; Simpson, R.J. Proteomics analysis of A33 immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature. Mol. Cell Proteomics 2010, 9, 197–208, doi:10.1074/mcp.M900152-MCP200.
[12]
Skog, J.; Wurdinger, T.; van Rijn, S.; Meijer, D.H.; Gainche, L.; Sena-Esteves, M.; Curry, W.T., Jr.; Carter, B.S.; Krichevsky, A.M.; Breakefield, X.O. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat. Cell Biol. 2008, 10, 1470–1476, doi:10.1038/ncb1800.
[13]
Muralidharan-Chari, V.; Clancy, J.; Plou, C.; Romao, M.; Chavrier, P.; Raposo, G.; D’Souza-Schorey, C. ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr. Biol. 2009, 19, 1875–1885, doi:10.1016/j.cub.2009.09.059.
[14]
Caby, M.P.; Lankar, D.; Vincendeau-Scherrer, C.; Raposo, G.; Bonnerot, C. Exosomal-like vesicles are present in human blood plasma. Int. Immunol. 2005, 17, 879–887, doi:10.1093/intimm/dxh267.
[15]
Inder, K.L.; Zheng, Y.Z.; Davis, M.J.; Moon, H.; Loo, D.; Nguyen, H.; Clements, J.A.; Parton, R.G.; Foster, L.J.; Hill, M.M. Expression of PTRF in PC-3 cells modulates cholesterol dynamics and the actin cytoskeleton impacting secretion pathways. Mol. Cell Proteomics 2012, 11, doi:10.1074/mcp.M111.012245.
[16]
Llorente, A.; de Marco, M.C.; Alonso, M.A. Caveolin-1 and MAL are located on prostasomes secreted by the prostate cancer PC-3 cell line. J. Cell Sci. 2004, 117, 5343–5351, doi:10.1242/jcs.01420.
Kalra, H.; Simpson, R.J.; Ji, H.; Aikawa, E.; Altevogt, P.; Askenase, P.; Bond, V.C.; Borras, F.E.; Breakefield, X.; Budnik, V.; et al. Vesiclepedia: A compendium for extracellular vesicles with continuous community annotation. PLoS Biol. 2012, 10, e1001450, doi:10.1371/journal.pbio.1001450.
[19]
Sotelo, J.R.; Porter, K.R. An electron microscope study of the rat ovum. J. Biophys. Biochem. Cytol. 1959, 5, 327–342, doi:10.1083/jcb.5.2.327.
[20]
Witwer, K.W.; Buzas, E.I.; Bemis, L.T.; Bora, A.; Lasser, C.; Lotvall, J.; Hoen, E.N.N.-T.; Piper, M.G.; Sivaraman, S.; Skog, J.; et al. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J. Extracell. Vesicles 2013, 2, doi:10.3402/jev.v2i0.20360.
[21]
Muralidharan-Chari, V.; Clancy, J.W.; Sedgwick, A.; D’Souza-Schorey, C. Microvesicles: Mediators of extracellular communication during cancer progression. J. Cell Sci. 2010, 123, 1603–1611, doi:10.1242/jcs.064386.
[22]
Hugel, B.; Martinez, M.C.; Kunzelmann, C.; Freyssinet, J.M. Membrane microparticles: Two sides of the coin. Physiology 2005, 20, 22–27, doi:10.1152/physiol.00029.2004.
[23]
Kueng, H.J.; Schmetterer, K.G.; Pickl, W.F. Lipid rafts, pseudotyping, and virus-like particles: Relevance of a novel, configurable, and modular antigen-presenting platform. Int. Arch. Allergy Immunol. 2011, 154, 89–110, doi:10.1159/000320224.
[24]
Nunez, R.; Sancho-Martinez, S.M.; Novoa, J.M.; Lopez-Hernandez, F.J. Apoptotic volume decrease as a geometric determinant for cell dismantling into apoptotic bodies. Cell Death Differ. 2010, 17, 1665–1671, doi:10.1038/cdd.2010.96.
[25]
Harding, C.V.; Heuser, J.E.; Stahl, P.D. Exosomes: Looking back three decades and into the future. J. Cell Biol. 2013, 200, 367–371, doi:10.1083/jcb.201212113.
[26]
Heijnen, H.F.; Schiel, A.E.; Fijnheer, R.; Geuze, H.J.; Sixma, J.J. 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.
[27]
Tauro, B.J.; Greening, D.W.; Mathias, R.A.; Ji, H.; Mathivanan, S.; Scott, A.M.; Simpson, R.J. Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods 2012, 56, 293–304, doi:10.1016/j.ymeth.2012.01.002.
[28]
Jansen, F.H.; Krijgsveld, J.; van Rijswijk, A.; van den Bemd, G.J.; van den Berg, M.S.; van Weerden, W.M.; Willemsen, R.; Dekker, L.J.; Luider, T.M.; Jenster, G. Exosomal secretion of cytoplasmic prostate cancer xenograft-derived proteins. Mol. Cell Proteomics 2009, 8, 1192–1205, doi:10.1074/mcp.M800443-MCP200.
[29]
Webber, J.; Clayton, A. How pure are your vesicles? J. Extracell. Vesicles 2013, 2, doi:10.3402/jev.v2i0.19861.
[30]
Nilsson, J.; Skog, J.; Nordstrand, A.; Baranov, V.; Mincheva-Nilsson, L.; Breakefield, X.O.; Widmark, A. Prostate cancer-derived urine exosomes: A novel approach to biomarkers for prostate cancer. Br. J. Cancer 2009, 100, 1603–1607, doi:10.1038/sj.bjc.6605058.
[31]
Ostrowski, M.; Carmo, N.B.; Krumeich, S.; Fanget, I.; Raposo, G.; Savina, A.; Moita, C.F.; Schauer, K.; Hume, A.N.; Freitas, R.P.; et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol. 2010, 12, 19–30, doi:10.1038/ncb2000.
[32]
Skriner, K.; Adolph, K.; Jungblut, P.R.; Burmester, G.R. Association of citrullinated proteins with synovial exosomes. Arthritis Rheum 2006, 54, 3809–3814, doi:10.1002/art.22276.
[33]
Bobrie, A.; Krumeich, S.; Reyal, F.; Recchi, C.; Moita, L.F.; Seabra, M.C.; Ostrowski, M.; Thery, C. Rab27a supports exosome-dependent and -independent mechanisms that modify the tumor microenvironment and can promote tumor progression. Cancer Res. 2012, 72, 4920–4930, doi:10.1158/0008-5472.CAN-12-0925.
[34]
Abache, T.; le Naour, F.; Planchon, S.; Harper, F.; Boucheix, C.; Rubinstein, E. The transferrin receptor and the tetraspanin web molecules CD9, CD81, and CD9P-1 are differentially sorted into exosomes after TPA treatment of K562 cells. J. Cell Biochem. 2007, 102, 650–664, doi:10.1002/jcb.21318.
[35]
Logozzi, M.; de Milito, A.; Lugini, L.; Borghi, M.; Calabro, L.; Spada, M.; Perdicchio, M.; Marino, M.L.; Federici, C.; Iessi, E.; et al. High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients. PLoS One 2009, 4, e5219, doi:10.1371/journal.pone.0005219.
[36]
Mathivanan, S.; Simpson, R.J. ExoCarta: A compendium of exosomal proteins and RNA. Proteomics 2009, 9, 4997–5000, doi:10.1002/pmic.200900351.
[37]
Kramer-Albers, E.M.; Bretz, N.; Tenzer, S.; Winterstein, C.; Mobius, W.; Berger, H.; Nave, K.A.; Schild, H.; Trotter, J. Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: Trophic support for axons? Proteomics Clin. Appl. 2007, 1, 1446–1461, doi:10.1002/prca.200700522.
[38]
Cabezas, A.; Bache, K.G.; Brech, A.; Stenmark, H. Alix regulates cortical actin and the spatial distribution of endosomes. J. Cell Sci. 2005, 118, 2625–2635, doi:10.1242/jcs.02382.
[39]
Welsch, S.; Habermann, A.; Jager, S.; Muller, B.; Krijnse-Locker, J.; Krausslich, H.G. Ultrastructuralanalysis of ESCRT proteins suggests a role for endosome-associated tubular-vesicular membranes in ESCRT function. Traffic 2006, 7, 1551–1566, doi:10.1111/j.1600-0854.2006.00489.x.
[40]
Deneka, M.; Pelchen-Matthews, A.; Byland, R.; Ruiz-Mateos, E.; Marsh, M. In macrophages, HIV-1 assembles into an intracellular plasma membrane domain containing the tetraspanins CD81, CD9, and CD53. J. Cell Biol. 2007, 177, 329–341, doi:10.1083/jcb.200609050.
[41]
Miyado, K.; Yamada, G.; Yamada, S.; Hasuwa, H.; Nakamura, Y.; Ryu, F.; Suzuki, K.; Kosai, K.; Inoue, K.; Ogura, A.; et al. Requirement of CD9 on the egg plasma membrane for fertilization. Science 2000, 287, 321–324, doi:10.1126/science.287.5451.321.
[42]
Nieuwenhuis, H.K.; van Oosterhout, J.J.; Rozemuller, E.; van Iwaarden, F.; Sixma, J.J. Studies with a monoclonal antibody against activated platelets: evidence that a secreted 53,000-molecular weight lysosome-like granule protein is exposed on the surface of activated platelets in the circulation. Blood 1987, 70, 838–845.
[43]
Toothill, V.J.; van Mourik, J.A.; Niewenhuis, H.K.; Metzelaar, M.J.; Pearson, J.D. Characterization of the enhanced adhesion of neutrophil leukocytes to thrombin-stimulated endothelial cells. J. Immunol. 1990, 145, 283–291.
[44]
Gross, C.N.; Irrinki, A.; Feder, J.N.; Enns, C.A. Co-trafficking of HFE, a nonclassical major histocompatibility complex class I protein, with the transferrin receptor implies a role in intracellular iron regulation. J. Biol. Chem. 1998, 273, 22068–22074, doi:10.1074/jbc.273.34.22068.
[45]
Katoh, K.; Shibata, H.; Hatta, K.; Maki, M. CHMP4b is a major binding partner of the ALG-2-interacting protein Alix among the three CHMP4 isoforms. Arch. Biochem. Biophys. 2004, 421, 159–165, doi:10.1016/j.abb.2003.09.038.
[46]
Strack, B.; Calistri, A.; Craig, S.; Popova, E.; Gottlinger, H.G. AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding. Cell 2003, 114, 689–699, doi:10.1016/S0092-8674(03)00653-6.
[47]
Hurley, J.H.; Odorizzi, G. Get on the exosome bus with ALIX. Nat. Cell Biol. 2012, 14, 654–655, doi:10.1038/ncb2530.
[48]
Hurley, J.H.; Hanson, P.I. Membrane budding and scission by the ESCRT machinery: It’s all in the neck. Nat. Rev. Mol. Cell Biol. 2010, 11, 556–566, doi:10.1038/nrm2937.
[49]
Gruenberg, J.; Stenmark, H. The biogenesis of multivesicular endosomes. Nat. Rev. Mol. Cell Biol. 2004, 5, 317–323, doi:10.1038/nrm1360.
[50]
Chatellard-Causse, C.; Blot, B.; Cristina, N.; Torch, S.; Missotten, M.; Sadoul, R. Alix (ALG-2-interacting protein X), a protein involved in apoptosis, binds to endophilins and induces cytoplasmic vacuolization. J. Biol. Chem. 2002, 277, 29108–29115.
[51]
Chen, B.; Borinstein, S.C.; Gillis, J.; Sykes, V.W.; Bogler, O. The glioma-associated protein SETA interacts with AIP1/Alix and ALG-2 and modulates apoptosis in astrocytes. J. Biol. Chem. 2000, 275, 19275–19281.
[52]
Schmidt, M.H.; Chen, B.; Randazzo, L.M.; Bogler, O. SETA/CIN85/Ruk and its binding partner AIP1 associate with diverse cytoskeletal elements, including FAKs, and modulate cell adhesion. J. Cell Sci. 2003, 116, 2845–2855, doi:10.1242/jcs.00522.
Radford, K.J.; Thorne, R.F.; Hersey, P. CD63 associates with transmembrane 4 superfamily members, CD9 and CD81, and with beta 1 integrins in human melanoma. Biochem. Biophys. Res. Commun. 1996, 222, 13–18, doi:10.1006/bbrc.1996.0690.
[55]
Israels, S.J.; McMillan-Ward, E.M. Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets. Thromb. Res. 2010, 125, 152–158, doi:10.1016/j.thromres.2009.07.005.
[56]
Maecker, H.T.; Todd, S.C.; Levy, S. The tetraspanin superfamily: Molecular facilitators. FASEB J. 1997, 11, 428–442.
[57]
Kotha, J.; Longhurst, C.; Appling, W.; Jennings, L.K. Tetraspanin CD9 regulates beta 1 integrin activation and enhances cell motility to fibronectin via a PI-3 kinase-dependent pathway. Exp. Cell Res. 2008, 314, 1811–1822, doi:10.1016/j.yexcr.2008.01.024.
[58]
Zhijun, X.; Shulan, Z.; Zhuo, Z. Expression and significance of the protein and mRNA of metastasis suppressor gene ME491/CD63 and integrin alpha5 in ovarian cancer tissues. Eur. J. Gynaecol. Oncol. 2007, 28, 179–183.
[59]
Chen, Z.; Mustafa, T.; Trojanowicz, B.; Brauckhoff, M.; Gimm, O.; Schmutzler, C.; Kohrle, J.; Holzhausen, H.J.; Kehlen, A.; Klonisch, T.; et al. CD82, and CD63 in thyroid cancer. Int. J. Mol. Med. 2004, 14, 517–527.
[60]
Barrio, M.M.; Portela, P.; Mordoh, J. Monoclonal antibody FC-5.01, directed against CD63 antigen, is internalized into cytoplasmic vesicles in the IIB-BR-G human breast cancer cell line. Hybridoma 1998, 17, 517–525, doi:10.1089/hyb.1998.17.517.
[61]
Chairoungdua, A.; Smith, D.L.; Pochard, P.; Hull, M.; Caplan, M.J. Exosome release of beta-catenin: A novel mechanism that antagonizes Wnt signaling. J. Cell Biol. 2010, 190, 1079–1091, doi:10.1083/jcb.201002049.
[62]
Kosaka, N.; Iguchi, H.; Yoshioka, Y.; Takeshita, F.; Matsuki, Y.; Ochiya, T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J. Biol. Chem. 2010, 285, 17442–17452, doi:10.1074/jbc.M110.107821.
[63]
Gould, S.J.; Booth, A.M.; Hildreth, J.E. The Trojan exosome hypothesis. Proc. Natl. Acad. Sci. USA 2003, 100, 10592–10597, doi:10.1073/pnas.1831413100.
[64]
Nabhan, J.F.; Hu, R.; Oh, R.S.; Cohen, S.N.; Lu, Q. Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. Proc. Natl. Acad. Sci. USA 2012, 109, 4146–4151, doi:10.1073/pnas.1200448109.
Fang, Y.; Wu, N.; Gan, X.; Yan, W.; Morrell, J.C.; Gould, S.J. Higher-order oligomerization targets plasma membrane proteins and HIV gag to exosomes. PLoS Biol. 2007, 5, e158, doi:10.1371/journal.pbio.0050158.
[67]
Bobrie, A.; Colombo, M.; Krumeich, S.; Raposo, G.; Thery, C. Diverse subpopulations of vesicles secreted by different intracellular mechanisms are present in exosome preparations obtained by differential ultracentrifugation. J. Extracell. Vesicles 2012, 1, doi:10.3402/jev.v1i0.18397.
[68]
Bobrie, A.; Thery, C. Exosomes and communication between tumours and the immune system: Are all exosomes equal? Biochem. Soc. Trans. 2013, 41, 263–267, doi:10.1042/BST20120245.
[69]
Duijvesz, D.; Luider, T.; Bangma, C.H.; Jenster, G. Exosomes as biomarker treasure chests for prostate cancer. Eur. Urol. 2011, 59, 823–831, doi:10.1016/j.eururo.2010.12.031.
[70]
Tarhan, F.; Orcun, A.; Kucukercan, I.; Camursoy, N.; Kuyumcuoglu, U. Effect of prostatic massage on serum complexed prostate-specific antigen levels. Urology 2005, 66, 1234–1238, doi:10.1016/j.urology.2005.06.077.
[71]
Thompson, I.M. PSA: A biomarker for disease. A biomarker for clinical trials. How useful is it? J. Nutr. 2006, 136, 2704S.
Stoorvogel, W.; Kleijmeer, M.J.; Geuze, H.J.; Raposo, G. The biogenesis and functions of exosomes. Traffic 2002, 3, 321–330, doi:10.1034/j.1600-0854.2002.30502.x.
[74]
Harding, C.; Heuser, J.; Stahl, P. Endocytosis and intracellular processing of transferrin and colloidal gold-transferrin in rat reticulocytes: Demonstration of a pathway for receptor shedding. Eur. J. Cell Biol. 1984, 35, 256–263.
[75]
Mohler, J.L.; Gregory, C.W.; Ford, O.H., 3rd; Kim, D.; Weaver, C.M.; Petrusz, P.; Wilson, E.M.; French, F.S. The androgen axis in recurrent prostate cancer. Clin. Cancer Res. 2004, 10, 440–448, doi:10.1158/1078-0432.CCR-1146-03.
[76]
Isaacs, J.T.; Coffey, D.S. Adaptation versus selection as the mechanism responsible for the relapse of prostatic cancer to androgen ablation therapy as studied in the Dunning R-3327-H adenocarcinoma. Cancer Res. 1981, 41, 5070–5075.
[77]
Heisler, L.E.; Evangelou, A.; Lew, A.M.; Trachtenberg, J.; Elsholtz, H.P.; Brown, T.J. Androgen-dependent cell cycle arrest and apoptotic death in PC-3 prostatic cell cultures expressing a full-length human androgen receptor. Mol. Cell Endocrinol. 1997, 126, 59–73, doi:10.1016/S0303-7207(96)03970-6.
[78]
Miyamoto, H.; Messing, E.M.; Chang, C. Androgen deprivation therapy for prostate cancer: Current status and future prospects. Prostate 2004, 61, 332–353, doi:10.1002/pros.20115.
[79]
Stridsberg, M.; Fabiani, R.; Lukinius, A.; Ronquist, G. Prostasomes are neuroendocrine-like vesicles in human semen. Prostate 1996, 29, 287–295, doi:10.1002/(SICI)1097-0045(199611)29:5<287::AID-PROS3>3.0.CO;2-7.
[80]
Arvidson, G.; Ronquist, G.; Wikander, G.; Ojteg, A.C. Human prostasome membranes exhibit very high cholesterol/phospholipid ratios yielding high molecular ordering. Biochim. Biophys. Acta 1989, 984, 167–173, doi:10.1016/0005-2736(89)90212-5.
Poliakov, A.; Spilman, M.; Dokland, T.; Amling, C.L.; Mobley, J.A. Structural heterogeneity and protein composition of exosome-like vesicles (prostasomes) in human semen. Prostate 2009, 69, 159–167, doi:10.1002/pros.20860.
[83]
Rooney, I.A.; Atkinson, J.P.; Krul, E.S.; Schonfeld, G.; Polakoski, K.; Saffitz, J.E.; Morgan, B.P. Physiologic relevance of the membrane attack complex inhibitory protein CD59 in human seminal plasma: CD59 is present on extracellular organelles (prostasomes), binds cell membranes, and inhibits complement-mediated lysis. J. Exp. Med. 1993, 177, 1409–1420, doi:10.1084/jem.177.5.1409.
[84]
Kitamura, M.; Namiki, M.; Matsumiya, K.; Tanaka, K.; Matsumoto, M.; Hara, T.; Kiyohara, H.; Okabe, M.; Okuyama, A.; Seya, T. Membrane cofactor protein (CD46) in seminal plasma is a prostasome-bound form with complement regulatory activity and measles virus neutralizing activity. Immunology 1995, 84, 626–632.
[85]
Rooney, I.A.; Heuser, J.E.; Atkinson, J.P. GPI-anchored complement regulatory proteins in seminal plasma. An analysis of their physical condition and the mechanisms of their binding to exogenous cells. J. Clin. Invest. 1996, 97, 1675–1686, doi:10.1172/JCI118594.
[86]
Wright, G.L., Jr.; Haley, C.; Beckett, M.L.; Schellhammer, P.F. Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. Urol. Oncol. 1995, 1, 18–28, doi:10.1016/1078-1439(95)00002-Y.
[87]
Moreno-Garcia, M.E.; Sumoza-Toledo, A.; Lund, F.E.; Santos-Argumedo, L. Localization of CD38 in murine B lymphocytes to plasma but not intracellular membranes. Mol. Immunol. 2005, 42, 703–711, doi:10.1016/j.molimm.2004.09.019.
[88]
Oliani, S.M.; Damazo, A.S.; Perretti, M. Annexin 1 localisation in tissue eosinophils as detected by electron microscopy. Mediators Inflamm. 2002, 11, 287–292, doi:10.1080/09629350210000015683.
[89]
Gorter, A.; Blok, V.T.; Haasnoot, W.H.; Ensink, N.G.; Daha, M.R.; Fleuren, G.J. Expression of CD46, CD55, and CD59 on renal tumor cell lines and their role in preventing complement-mediated tumor cell lysis. Lab. Invest. 1996, 74, 1039–1049.
[90]
Cattaneo, R. Four viruses, two bacteria, and one receptor: membrane cofactor protein (CD46) as pathogens’ magnet. J. Virol. 2004, 78, 4385–4388, doi:10.1128/JVI.78.9.4385-4388.2004.
[91]
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, doi:10.1016/j.ejcb.2007.05.001.
[92]
Thery, C.; Ostrowski, M.; Segura, E. Membrane vesicles as conveyors of immune responses. Nat. Rev. Immunol. 2009, 9, 581–593, doi:10.1038/nri2567.
[93]
Mitchell, P.J.; Welton, J.; Staffurth, J.; Court, J.; Mason, M.D.; Tabi, Z.; Clayton, A. Can urinary exosomes act as treatment response markers in prostate cancer? J. Transl. Med. 2009, 7, doi:10.1186/1479-5876-7-4.
[94]
Gonzalez-Begne, M.; Lu, B.; Liao, L.; Xu, T.; Bedi, G.; Melvin, J.E.; Yates, J.R., 3rd. Characterization of the human submandibular/sublingual saliva glycoproteome using lectin affinity chromatography coupled to multidimensional protein identification technology. J. Proteome Res. 2011, 10, 5031–5046, doi:10.1021/pr200505t.
[95]
Gonzalez-Begne, M.; Lu, B.; Han, X.; Hagen, F.K.; Hand, A.R.; Melvin, J.E.; Yates, J.R. Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). J. Proteome Res. 2009, 8, 1304–1314, doi:10.1021/pr800658c.
[96]
Perner, S.; Hofer, M.D.; Kim, R.; Shah, R.B.; Li, H.; Moller, P.; Hautmann, R.E.; Gschwend, J.E.; Kuefer, R.; Rubin, M.A. Prostate-specific membrane antigen expression as a predictor of prostate cancer progression. Hum. Pathol. 2007, 38, 696–701, doi:10.1016/j.humpath.2006.11.012.
[97]
Hara, N.; Kasahara, T.; Kawasaki, T.; Bilim, V.; Obara, K.; Takahashi, K.; Tomita, Y. Reverse transcription-polymerase chain reaction detection of prostate-specific antigen, prostate-specific membrane antigen, and prostate stem cell antigen in one milliliter of peripheral blood: value for the staging of prostate cancer. Clin. Cancer Res. 2002, 8, 1794–1799.
[98]
Bouchelouche, K.; Choyke, P.L.; Capala, J. Prostate specific membrane antigen—A target for imaging and therapy with radionuclides. Discov. Med. 2010, 9, 55–61.
[99]
Sodee, D.B.; Ellis, R.J.; Samuels, M.A.; Spirnak, J.P.; Poole, W.F.; Riester, C.; Martanovic, D.M.; Stonecipher, R.; Bellon, E.M. Prostate cancer and prostate bed SPECT imaging with ProstaScint: Semiquantitative correlation with prostatic biopsy results. Prostate 1998, 37, 140–148, doi:10.1002/(SICI)1097-0045(19981101)37:3<140::AID-PROS3>3.0.CO;2-Q.
[100]
Jemaa, A.B.; Bouraoui, Y.; Sallami, S.; Banasr, A.; Nouira, Y.; Oueslati, R. Psma/Psa ratio evaluated by immunohistochemistry may improve diagnosis of prostate cancer. J. Immunoassay Immunochem. 2014, 35, 48–59, doi:10.1080/15321819.2013.792830.
[101]
Phin, S.; Moore, M.W.; Cotter, P.D. Genomic rearrangements of PTEN in prostate cancer. Front. Oncol. 2013, 3, doi:10.3389/fonc.2013.00240.
[102]
Gabriel, K.; Ingram, A.; Austin, R.; Kapoor, A.; Tang, D.; Majeed, F.; Qureshi, T.; Al-Nedawi, K. Regulation of the Tumor suppressor PTEN through exosomes: A diagnostic potential for prostate cancer. PLoS One 2013, 8, e70047.
[103]
Higashiyama, M.; Taki, T.; Ieki, Y.; Adachi, M.; Huang, C.L.; Koh, T.; Kodama, K.; Doi, O.; Miyake, M. Reduced motility related protein-1 (MRP-1/CD9) gene expression as a factor of poor prognosis in non-small cell lung cancer. Cancer Res. 1995, 55, 6040–6044.
[104]
Miyake, M.; Nakano, K.; Itoi, S.I.; Koh, T.; Taki, T. Motility-related protein-1 (MRP-1/CD9) reduction as a factor of poor prognosis in breast cancer. Cancer Res. 1996, 56, 1244–1249.
[105]
Copeland, B.T.; Bowman, M.J.; Boucheix, C.; Ashman, L.K. Knockout of the tetraspanin Cd9 in the TRAMP model of de novo prostate cancer increases spontaneous metastases in an organ-specific manner. Int. J. Cancer 2013, 133, 1803–1812, doi:10.1002/ijc.28204.
[106]
Kohmo, S.; Kijima, T.; Otani, Y.; Mori, M.; Minami, T.; Takahashi, R.; Nagatomo, I.; Takeda, Y.; Kida, H.; Goya, S.; et al. Cell surface tetraspanin CD9 mediates chemoresistance in small cell lung cancer. Cancer Res. 2010, 70, 8025–8035, doi:10.1158/0008-5472.CAN-10-0996.
[107]
Navone, N.M.; Troncoso, P.; Pisters, L.L.; Goodrow, T.L.; Palmer, J.L.; Nichols, W.W.; von Eschenbach, A.C.; Conti, C.J. p53 protein accumulation and gene mutation in the progression of human prostate carcinoma. J. Natl. Cancer Inst. 1993, 85, 1657–1669, doi:10.1093/jnci/85.20.1657.
[108]
Bookstein, R.; MacGrogan, D.; Hilsenbeck, S.G.; Sharkey, F.; Allred, D.C. p53 is mutated in a subset of advanced-stage prostate cancers. Cancer Res. 1993, 53, 3369–3373.
[109]
Yu, X.; Harris, S.L.; Levine, A.J. The regulation of exosome secretion: A novel function of the p53 protein. Cancer Res. 2006, 66, 4795–4801, doi:10.1158/0008-5472.CAN-05-4579.
[110]
Carayon, K.; Chaoui, K.; Ronzier, E.; Lazar, I.; Bertrand-Michel, J.; Roques, V.; Balor, S.; Terce, F.; Lopez, A.; Salome, L.; et al. Proteolipidic composition of exosomes changes during reticulocyte maturation. J. Biol. Chem. 2011, 286, 34426–34439, doi:10.1074/jbc.M111.257444.
[111]
Gonzales, P.A.; Pisitkun, T.; Hoffert, J.D.; Tchapyjnikov, D.; Star, R.A.; Kleta, R.; Wang, N.S.; Knepper, M.A. Large-scale proteomics and phosphoproteomics of urinary exosomes. J. Am. Soc. Nephrol. 2009, 20, 363–379, doi:10.1681/ASN.2008040406.
[112]
Pisitkun, T.; Shen, R.F.; Knepper, M.A. Identification and proteomic profiling of exosomes in human urine. Proc. Natl. Acad. Sci. USA 2004, 101, 13368–13373, doi:10.1073/pnas.0403453101.
[113]
Tomlins, S.A.; Rhodes, D.R.; Perner, S.; Dhanasekaran, S.M.; Mehra, R.; Sun, X.W.; Varambally, S.; Cao, X.; Tchinda, J.; Kuefer, R.; et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005, 310, 644–648, doi:10.1126/science.1117679.
[114]
Lapointe, J.; Kim, Y.H.; Miller, M.A.; Li, C.; Kaygusuz, G.; van de Rijn, M.; Huntsman, D.G.; Brooks, J.D.; Pollack, J.R. A variant TMPRSS2 isoform and ERG fusion product in prostate cancer with implications for molecular diagnosis. Mod. Pathol. 2007, 20, 467–473, doi:10.1038/modpathol.3800759.
[115]
Wang, J.; Cai, Y.; Ren, C.; Ittmann, M. Expression of variant TMPRSS2/ERG fusion messenger RNAs is associated with aggressive prostate cancer. Cancer Res. 2006, 66, 8347–8351, doi:10.1158/0008-5472.CAN-06-1966.
[116]
Narayanan, R.; Jiang, J.; Gusev, Y.; Jones, A.; Kearbey, J.D.; Miller, D.D.; Schmittgen, T.D.; Dalton, J.T. MicroRNAs are mediators of androgen action in prostate and muscle. PLoS One 2010, 5, e13637, doi:10.1371/journal.pone.0013637.
[117]
Lim, L.P.; Lau, N.C.; Garrett-Engele, P.; Grimson, A.; Schelter, J.M.; Castle, J.; Bartel, D.P.; Linsley, P.S.; Johnson, J.M. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 2005, 433, 769–773, doi:10.1038/nature03315.
[118]
Song, J.J.; Smith, S.K.; Hannon, G.J.; Joshua-Tor, L. Crystal structure of Argonaute and its implications for RISC slicer activity. Science 2004, 305, 1434–1437, doi:10.1126/science.1102514.
[119]
Carrington, J.C.; Ambros, V. Role of microRNAs in plant and animal development. Science 2003, 301, 336–338, doi:10.1126/science.1085242.
[120]
Meister, G. miRNAs get an early start on translational silencing. Cell 2007, 131, 25–28, doi:10.1016/j.cell.2007.09.021.
[121]
Gibbings, D.J.; Ciaudo, C.; Erhardt, M.; Voinnet, O. Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat. Cell Biol. 2009, 11, 1143–1149, doi:10.1038/ncb1929.
[122]
Mitchell, P.S.; Parkin, R.K.; Kroh, E.M.; Fritz, B.R.; Wyman, S.K.; Pogosova-Agadjanyan, E.L.; Peterson, A.; Noteboom, J.; O’Briant, K.C.; Allen, A.; et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. USA 2008, 105, 10513–10518, doi:10.1073/pnas.0804549105.
[123]
Bryant, R.J.; Pawlowski, T.; Catto, J.W.; Marsden, G.; Vessella, R.L.; Rhees, B.; Kuslich, C.; Visakorpi, T.; Hamdy, F.C. Changes in circulating microRNA levels associated with prostate cancer. Br. J. Cancer 2012, 106, 768–774, doi:10.1038/bjc.2011.595.
[124]
Moltzahn, F.; Olshen, A.B.; Baehner, L.; Peek, A.; Fong, L.; Stoppler, H.; Simko, J.; Hilton, J.F.; Carroll, P.; Blelloch, R. Microfluidic-based multiplex qRT-PCR identifies diagnostic and prognostic microRNA signatures in the sera of prostate cancer patients. Cancer Res. 2011, 71, 550–560, doi:10.1158/0008-5472.CAN-10-1229.
[125]
Sita-Lumsden, A.; Dart, D.A.; Waxman, J.; Bevan, C.L. Circulating microRNAs as potential new biomarkers for prostate cancer. Br. J. Cancer 2013, 108, 1925–1930, doi:10.1038/bjc.2013.192.
[126]
Waltering, K.K.; Porkka, K.P.; Jalava, S.E.; Urbanucci, A.; Kohonen, P.J.; Latonen, L.M.; Kallioniemi, O.P.; Jenster, G.; Visakorpi, T. Androgen regulation of micro-RNAs in prostate cancer. Prostate 2011, 71, 604–614, doi:10.1002/pros.21276.
[127]
Hessvik, N.P.; 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, doi:10.1016/j.bbagrm.2012.08.016.
[128]
Corcoran, C.; Rani, S.; O’Brien, K.; O’Neill, A.; Prencipe, M.; Sheikh, R.; Webb, G.; McDermott, R.; Watson, W.; Crown, J.; et al. Docetaxel-resistance in prostate cancer: Evaluating associated phenotypic changes and potential for resistance transfer via exosomes. PLoS One 2012, 7, e50999, doi:10.1371/journal.pone.0050999.
[129]
Mohan, K.V.; Devadas, K.; Sainath Rao, S.; Hewlett, I.; Atreya, C. Identification of XMRV infection-associated microRNAs in four cell types in culture. PLoS One 2012, 7, e32853.
[130]
Knouf, E.C.; Metzger, M.J.; Mitchell, P.S.; Arroyo, J.D.; Chevillet, J.R.; Tewari, M.; Miller, A.D. Multiple integrated copies and high-level production of the human retrovirus XMRV (xenotropic murine leukemia virus-related virus) from 22Rv1 prostate carcinoma cells. J. Virol. 2009, 83, 7353–7356, doi:10.1128/JVI.00546-09.
[131]
Hosseini-Beheshti, E.; Pham, S.; Adomat, H.; Li, N.; Guns, E.S. Exosomes as biomarker enriched microvesicles: Characterization of exosomal proteins derived from a panel of prostate cell lines with distinct AR phenotypes. Mol. Cell. Proteomics 2012, 11, 863–885, doi:10.1074/mcp.M111.014845.
[132]
Llorente, A.; Skotland, T.; Sylvanne, T.; Kauhanen, D.; Rog, T.; Orlowski, A.; Vattulainen, I.; Ekroos, K.; Sandvig, K. Molecular lipidomics of exosomes released by PC-3 prostate cancer cells. Biochim. Biophys. Acta 2013, 1831, 1302–1309, doi:10.1016/j.bbalip.2013.04.011.
[133]
Gruenberg, J. The endocytic pathway: A mosaic of domains. Nat. Rev. Mol. Cell Biol. 2001, 2, 721–730, doi:10.1038/35096054.
[134]
Dikic, I. ALIX-ing phospholipids with endosome biogenesis. Bioessays 2004, 26, 604–607, doi:10.1002/bies.20068.
[135]
Matsuo, H.; Chevallier, J.; Mayran, N.; le Blanc, I.; Ferguson, C.; Faure, J.; Blanc, N.S.; Matile, S.; Dubochet, J.; Sadoul, R.; et al. Role of LBPA and Alix in multivesicular liposome formation and endosome organization. Science 2004, 303, 531–534, doi:10.1126/science.1092425.
Karam, J.A.; Lotan, Y.; Roehrborn, C.G.; Ashfaq, R.; Karakiewicz, P.I.; Shariat, S.F. Caveolin-1 overexpression is associated with aggressive prostate cancer recurrence. Prostate 2007, 67, 614–622, doi:10.1002/pros.20557.
[138]
Shvartsman, D.E.; Gutman, O.; Tietz, A.; Henis, Y.I. Cyclodextrins but not compactin inhibit the lateral diffusion of membrane proteins independent of cholesterol. Traffic 2006, 7, 917–926, doi:10.1111/j.1600-0854.2006.00437.x.
[139]
Goodwin, J.S.; Drake, K.R.; Remmert, C.L.; Kenworthy, A.K. Ras diffusion is sensitive to plasma membrane viscosity. Biophys. J. 2005, 89, 1398–1410, doi:10.1529/biophysj.104.055640.
[140]
Broquet, A.H.; Thomas, G.; Masliah, J.; Trugnan, G.; Bachelet, M. Expression of the molecular chaperone Hsp70 in detergent-resistant microdomains correlates with its membrane delivery and release. J. Biol. Chem. 2003, 278, 21601–21606.
[141]
Lancaster, G.I.; Febbraio, M.A. Exosome-dependent trafficking of HSP70: A novel secretory pathway for cellular stress proteins. J. Biol. Chem. 2005, 280, 23349–23355, doi:10.1074/jbc.M502017200.
[142]
Szafranska-Schwarzbach, A.E.; Adai, A.T.; Lee, L.S.; Conwell, D.L.; Andruss, B.F. Development of a miRNA-based diagnostic assay for pancreatic ductal adenocarcinoma. Expert Rev. Mol. Diagn. 2011, 11, 249–257.
