Prostasomes

Prostasomes were discovered in 1978 as submicron membranous vesicles (40-500 nm in diameter) secreted by the prostate gland epithelial cells into seminal fluid.[1] They possess an unusual lipid composition and a tight and highly ordered structure of their lipoprotein membranes resembling lipid raft. The physiological role of prostasomes implicates improvement of sperm motility and protection against attacks from the female immune defense during the passage to the egg.[2]

Investigations have shown that cancerous prostate cells and prostate cells with low differentiation continue to produce and secrete prostasomes.[3] The high incidence of prostate cancer in elderly men could take advantage of the immune protective activities supported by the prostasomes.

Immune regulating proteins found in prostasomes include: amino-peptidase N (CD13); dipeptidyl-peptidase IV (CD26); enkephalinase (neutral endopeptidase, CD10); angiotensin converting enzyme (ACE, CD143); tissue factor TF (CD142, thromboplastin); decay accelerating factor (CD55); protectin (CD59, inhibitor of MAC) and complement regulatory membrane cofactor protein (CD46).[4][5][6] Prostasomes also contain high levels of the divalent cations: Zn2+, Ca2+ and Mg2+.

Historical background of prostasome research

Year
1977-78 An ATPase activity in seminal plasma indicated an occurrence of membrane-surrounded extracellular vesicles [7][8][9]
1981 The first association between prostasomes and fertility was reported [10]
1982 The name prostasomes was coined (prosta-prostate; somes [Greek “soma”]-body) and the first functional study of prostasomes was performed [11][12][13][14][15]
1983 The first electron microscopic pictures of prostasomes inside storage vesicles (multivesicular bodies) in cytoplasm of prostate epithelial cells and their extracellular release into lumen of the prostate [16][17]
1984 The role of prostasomes in infertility and prostate cancer was investigated [18]
1985 The first comprehensive review of prostasomes was published in Biochim Biophys Acta [19]
1986-89 Studies on ATPases on the prostasomal surface [20][21][22][23]
1989 The prostasomal membrane was found to have a much higher cholesterol/phospholipid ratio than ordinary cellular membranes [24]
1990 Nucleic acid was found to be associated with prostasomes.[25] An interaction between prostasomes and sperm was shown [26]
1991-94 Prostasomes and their role in immunosuppression were investigated in several articles.[27][28][29] Granulophysin (CD63) was suggested as a marker for prostasomes[30]
1995-2001 Monoclonal antibodies against prostasomes were produced and several studies involving these antibodies were performed [31][32][33] as well as prostasome-sperm interaction studies.[34][35][36][37][38][39] Prostasomes were discovered in prostatic fluid of other species.[40][41] Prostatic cancer cell lines were found to produce prostasomes.[42][43] Prostasomes displayed anti-bacterial activity[44]
2001 An international symposium on prostasomes was held at Wenner-Gren Centre in Stockholm[45]
2001 Autoantibodies against prostasomes were evaluated as biomarkers for prostate cancer [46]
2003 The first comprehensive shotgun proteomics of the prostasome proteome [47] and it has been followed by two others [48][49]
2005 Haemostasis coupled to prostasomes and the prostasomal membrane in fertility and in cancer [50][51][52]
2009- Investigation of prostasomal DNA.[53][54][55] DNA was found in both non-malignant prostasomes as well as in prostate cancer (PC3) cell derived prostasomes/exosomes [53]
2009- Prostasomes as a serum biomarker of prostate cancer [56]

References

  1. ↑ Ronquist G, Brody I (1985). "The prostasome: its secretion and function in man.". Biochim Biophys Acta. 822 (2): 203–18. doi:10.1016/0304-4157(85)90008-5. PMID 2992593.
  2. ↑ Burden HP, Holmes CH, Persad R, Whittington K (2006). "Prostasomes--their effects on human male reproduction and fertility.". Hum Reprod Update. 12 (3): 283–92. doi:10.1093/humupd/dmi052. PMID 16373403.
  3. ↑ Ronquist G, Nilsson BO (2004). "The Janus-faced nature of prostasomes: their pluripotency favours the normal reproductive process and malignant prostate growth.". Prostate Cancer Prostatic Dis. 7 (1): 21–31. doi:10.1038/sj.pcan.4500684. PMID 14999234.
  4. ↑ Ronquist, G., Jin, M., Schrimpf, S. and Nilsson, B. O. (Motta, P. M. ed.) (1997) Prostasomes and human reproduction. Microscopy of Reproduction and Development: A Dynamic Approach pp. 213-219. Antonio Delfino Editore, Rome
  5. ↑ Ronquist, G., Carlsson, L., Larsson, A. and Nilsson, B. O. (Ronquist, G. and Nilsson, B. O. eds.) (2002) Prostasomes. Prostasomes: Proceedings from a symposium held at the Wenner-Gren Centre, Stockholm, June 2001 pp. 1-9. Portland Press, London
  6. ↑ Stewart AB, Anderson W, Delves G, Lwaleed BA, Birch B, Cooper A (2004). "Prostasomes: a role in prostatic disease?". BJU Int. 94 (4): 985–9. doi:10.1111/j.1464-410X.2004.05091.x. PMID 15541114.
  7. ↑ Ronquist, G; Hedström, M (1977). [PM:142513 "Restoration of detergent-inactivated adenosine triphosphatase activity of human prostatic fluid with concanavalin A"] Check |url= value (help). Biochim. Biophys. Acta. 483 (2): 483–486. doi:10.1016/0005-2744(77)90078-x. PMID 142513.
  8. ↑ Ronquist, G; Brody, I; Gottfries, A; Stegmayr, B (1978). [PM:152589 "An Mg2+ and Ca2+-stimulated adenosine triphosphatase in human prostatic fluid: part I"] Check |url= value (help). Andrologia. 10 (4): 261–272. doi:10.1111/j.1439-0272.1978.tb03030.x. PMID 152589.
  9. ↑ Ronquist, G; Brody, I; Gottfries, A; Stegmayr, B (1978). [PM:153718 "An Mg2+ and Ca2+-stimulated adenosine triphosphatase in human prostatic fluid--part II"] Check |url= value (help). Andrologia. 10 (6): 427–433. doi:10.1111/j.1439-0272.1978.tb03064.x. PMID 153718.
  10. ↑ Brody, I; Ronquist, G; Gottfries, A; Stegmayr, B (1981). [PM:6120566 "Abnormal deficiency of both Mg2+ and Ca2+-dependent adenosine triphosphatase and secretory granules and vesicles in human seminal plasma"] Check |url= value (help). Scand. J. Urol. Nephrol. 15 (2): 85–90. doi:10.3109/00365598109179581. PMID 6120566.
  11. ↑ Stegmayr, B; Brody, I; Ronquist, G (1982). [PM:6283103 "A biochemical and ultrastructural study on the endogenous protein kinase activity of secretory granule membranes of prostatic origin in human seminal plasma"] Check |url= value (help). J. Ultrastruct. Res. 78 (2): 206–214. doi:10.1016/s0022-5320(82)80024-5. PMID 6283103.
  12. ↑ Stegmayr, B; Ronquist, G (1982). [PM:7123173 "Stimulation of sperm progressive motility by organelles in human seminal plasma"] Check |url= value (help). Scand. J. Urol. Nephrol. 16 (2): 85–90. doi:10.3109/00365598209179734. PMID 7123173.
  13. ↑ Stegmayr, B; Ronquist, G (1982). [PM:6289426 "Distribution of cyclic AMP in human seminal plasma and its relation to sperm progressive motility"] Check |url= value (help). Scand. J. Urol. Nephrol. 16 (2): 91–95. doi:10.3109/00365598209179735. PMID 6289426.
  14. ↑ Stegmayr, B; Ronquist, G (1982). [PM:6219486 "Promotive effect on human sperm progressive motility by prostasomes"] Check |url= value (help). Urol. Res. 10 (5): 253–257. doi:10.1007/bf00255932. PMID 6219486.
  15. ↑ Stegmayr, B; Berggren, PO; Ronquist, G; Hellman, B (1982). [PM:6219456 "Calcium, magnesium, and zinc contents in organelles of prostatic origin in human seminal plasma"] Check |url= value (help). Scand. J. Urol. Nephrol. 16 (3): 199–203. doi:10.3109/00365598209179753. PMID 6219456.
  16. ↑ Ronquist, G; Stegmayr, B; Brody, I; Gottfries, A (1983). [PM:6865591 "[Prostasomes--a newly discovered organelle that increases sperm motility]"] Check |url= value (help). Lakartidningen. 80 (9): 810–813. PMID 6865591.
  17. ↑ Brody, I; Ronquist, G; Gottfries, A (1983). [PM:6649193 "Ultrastructural localization of the prostasome - an organelle in human seminal plasma"] Check |url= value (help). Ups. J. Med. Sci. 88 (2): 63–80. doi:10.3109/03009738309178440. PMID 6649193.
  18. ↑ Ronquist, G; Stegmayr, B (1984). [PM:6240149 "Prostatic origin of fucosyl transferase in human seminal plasma--a study on healthy controls and on men with infertility or with prostatic cancer"] Check |url= value (help). Urol. Res. 12 (5): 243–247. doi:10.1007/bf00256148. PMID 6240149.
  19. ↑ Ronquist, G; Brody, I (1985). [PM:2992593 "The prostasome: its secretion and function in man"] Check |url= value (help). Biochim. Biophys. Acta. 822 (2): 203–218. doi:10.1016/0304-4157(85)90008-5. PMID 2992593.
  20. ↑ Ronquist, G; Frithz, GG (1986). [PM:3577591 "Prostasomes in human semen contain ADP and GDP"] Check |url= value (help). Acta Eur. Fertil. 17 (4): 273–276. PMID 3577591.
  21. ↑ Ronquist, G (1987). [PM:2957209 "Effect of modulators on prostasome membrane-bound ATPase in human seminal plasma"] Check |url= value (help). Eur. J. Clin. Invest. 17 (3): 231–236. doi:10.1111/j.1365-2362.1987.tb01241.x. PMID 2957209.
  22. ↑ Ronquist, G (1988). [PM:2977004 "Zinc ion stimulation of ATP cleavage by prostasomes from human seminal plasma"] Check |url= value (help). Urol. Int. 43 (6): 334–340. doi:10.1159/000281386. PMID 2977004.
  23. ↑ Ronquist, G; Frithz, G; Jansson, A (1988). [PM:2902707 "Prostasome membrane associated enzyme activities and semen parameters in men attending an infertility clinic"] Check |url= value (help). Urol. Int. 43 (3): 133–138. doi:10.1159/000281325. PMID 2902707.
  24. ↑ Arvidson, Gösta; Ronquist, Gunnar; Wikander, Göran; Öjteg, Anna-Carin (September 1989). [PM:2548623 "Human prostasome membranes exhibit very high cholesterol/phospholipid ratios yielding high molecular ordering"] Check |url= value (help). Biochimica et Biophysica Acta (BBA) - Biomembranes. 984 (2): 167–173. doi:10.1016/0005-2736(89)90212-5. PMID 2548623.
  25. ↑ Olsson, I; Ronquist, G (1990). [PM:1691619 "Nucleic acid association to human prostasomes"] Check |url= value (help). Arch. Androl. 24 (1): 1–10. doi:10.3109/01485019008986852. PMID 1691619.
  26. ↑ Ronquist, G; Nilsson, BO; Hjerten, S (1990). [PM:2327824 "Interaction between prostasomes and spermatozoa from human semen"] Check |url= value (help). Arch. Androl. 24 (2): 147–157. doi:10.3109/01485019008986874. PMID 2327824.
  27. ↑ Kelly, RW; Holland, P; Skibinski, G; Harrison, C; McMillan, L; Hargreave, T; James, K (1991). [PM:1747961 "Extracellular organelles (prostasomes) are immunosuppressive components of human semen"] Check |url= value (help). Clin. Exp. Immunol. 86 (3): 550–556. doi:10.1111/j.1365-2249.1991.tb02968.x. PMID 1747961.
  28. ↑ Skibinski, G; Kelly, RW; Harkiss, D; James, K (1992). [PM:1337434 "Immunosuppression by human seminal plasma--extracellular organelles (prostasomes) modulate activity of phagocytic cells"] Check |url= value (help). Am. J. Reprod. Immunol. 28 (2): 97–103. doi:10.1111/j.1600-0897.1992.tb00767.x. PMID 1337434.
  29. ↑ Rooney, IA; Atkinson, JP; Krul, ES; Schonfeld, G; Polakoski, K; Saffitz, JE; Morgan, BP (1993). [PM:7683035 "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"] Check |url= value (help). J. Exp. Med. 177 (5): 1409–1420. doi:10.1084/jem.177.5.1409. PMID 7683035.
  30. ↑ Skibinski, G; Kelly, RW; James, K (1994). [PM:8150122 "Expression of a common secretory granule specific protein as a marker for the extracellular organelles (prostasomes) in human semen"] Check |url= value (help). Fertil. Steril. 61 (4): 755–759. doi:10.1016/s0015-0282(16)56658-8. PMID 8150122.
  31. ↑ Ronquist, G; Fabiani, R; Jin, M; Nilsson, BO; Elenbring, K; Hjerten, S (1996). [PM:8907670 "Adherence of human prostasomes to mouse spermatozoa and their displacement by monoclonal antibodies as revealed by free zone electrophoresis"] Check |url= value (help). Arch. Androl. 36 (2): 101–107. doi:10.3109/01485019608987085. PMID 8907670.
  32. ↑ Nilsson, BO; Jin, M; Ronquist, G (1996). [PM:8897705 "Immunolocalization of prostasomes in the human prostate"] Check |url= value (help). Ups. J. Med. Sci. 101 (2): 149–157. doi:10.3109/03009739609178919. PMID 8897705.
  33. ↑ Nilsson, B. Ove; Jin, Meishan; Einarsson, Barbro; Persson, Bo-Eric; Ronquist, Gunnar (15 May 1998). [PM:9582086 "Monoclonal antibodies against human prostasomes"] Check |url= value (help). The Prostate. 35 (3): 178–184. doi:10.1002/(SICI)1097-0045(19980515)35:3<178::AID-PROS3>3.0.CO;2-D. PMID 9582086.
  34. ↑ Arienti, G; Carlini, E; Verdacchi, R; Cosmi, EV; Palmerini, CA (1997). [PM:9367181 "Prostasome to sperm transfer of CD13/aminopeptidase N (EC 3.4.11.2)"] Check |url= value (help). Biochim. Biophys. Acta. 1336 (3): 533–538. doi:10.1016/s0304-4165(97)00071-8. PMID 9367181.
  35. ↑ Arienti, Giuseppe; Carlini, Enrico; Verdacchi, Rosaria; Palmerini, Carlo A (August 1997). [PM:9305799 "Transfer of aminopeptidase activity from prostasomes to sperm"] Check |url= value (help). Biochimica et Biophysica Acta (BBA) - General Subjects. 1336 (2): 269–274. doi:10.1016/S0304-4165(97)00036-6. PMID 9305799.
  36. ↑ Carlini, Enrico; Palmerini, Carlo Alberto; Cosmi, Ermelando Vinicio; Arienti, Giuseppe (July 1997). [PM:9210640 "Fusion of Sperm with Prostasomes: Effects on Membrane Fluidity"] Check |url= value (help). Archives of Biochemistry and Biophysics. 343 (1): 6–12. doi:10.1006/abbi.1997.9999. PMID 9210640.
  37. ↑ Arienti, Giuseppe; Polci, Andrea; Carlini, Enrico; Palmerini, Carlo A (June 1997). [PM:9237659 "Transfer of CD26/dipeptidyl peptidaseIV (E.C. 3.5.4.4) from prostasomes to sperm"] Check |url= value (help). FEBS Letters. 410 (2-3): 343–346. doi:10.1016/S0014-5793(97)00655-8. PMID 9237659.
  38. ↑ Arienti, G.; Carlini, E.; Palmerini, C.A. (1 January 1997). [PM:9002427 "Fusion of Human Sperm to Prostasomes at Acidic pH"] Check |url= value (help). Journal of Membrane Biology. 155 (1): 89–94. doi:10.1007/s002329900160. PMID 9002427.
  39. ↑ Renneberg, Heiner; Konrad, Lutz; Dammshäuser, Irmgard; Seitz, Jürgen; Aumüller, Gerhard (1 February 1997). [PM:9051148 "Immunohistochemistry of prostasomes from human semen"] Check |url= value (help). The Prostate. 30 (2): 98–106. doi:10.1002/(SICI)1097-0045(19970201)30:2<98::AID-PROS5>3.0.CO;2-G. PMID 9051148.
  40. ↑ Arienti, G; Carlini, E; De Cosmo, AM; DiProfio, P; Palmerini, CA (1998). [PM:9687300 "Prostasome-like particles in stallion semen"] Check |url= value (help). Biol. Reprod. 59 (2): 309–313. doi:10.1095/biolreprod59.2.309. PMID 9687300.
  41. ↑ Minelli, A; Moroni, M; Martinez, E; Mezzasoma, I; Ronquist, G (1998). [PM:10070353 "Occurrence of prostasome-like membrane vesicles in equine seminal plasma"] Check |url= value (help). J. Reprod. Fertil. 114 (2): 237–243. doi:10.1530/jrf.0.1140237. PMID 10070353.
  42. ↑ Nilsson, BO; Lennartsson, L; Carlsson, L; Nilsson, S; Ronquist, G (1999). [PM:10680953 "Expression of prostasome-like granules by the prostate cancer cell lines PC3, Du145 and LnCaP grown in monolayer"] Check |url= value (help). Ups. J. Med. Sci. 104 (3): 199–206. doi:10.3109/03009739909178963. PMID 10680953.
  43. ↑ Nilsson, B. Ove; Egevad, Lars; Jin, Meishan; Ronquist, Gunnar; Busch, Christer (1 April 1999). [PM:10221264 "Distribution of prostasomes in neoplastic epithelial prostate cells"] Check |url= value (help). The Prostate. 39 (1): 36–40. doi:10.1002/(SICI)1097-0045(19990401)39:1<36::AID-PROS6>3.0.CO;2-6. PMID 10221264.
  44. ↑ Carlsson, Lena; Påhlson, Carl; Bergquist, Magnus; Ronquist, Gunnar; Stridsberg, Mats (1 September 2000). [PM:10951492 "Antibacterial activity of human prostasomes"] Check |url= value (help). The Prostate. 44 (4): 279–286. doi:10.1002/1097-0045(20000901)44:4<279::AID-PROS4>3.0.CO;2-2. PMID 10951492.
  45. ↑ Nilsson, edited by G. Ronquist, B.O. (2002). Prostasomes : proceedings from a symposium held at the Wenner-Gren Centre, Stockholm, in June 2001. London: Portland. ISBN 9781855781511.
  46. ↑ Nilsson, BO; Carlsson, L; Larsson, A; Ronquist, G (2001). [PM:11817562 "Autoantibodies to prostasomes as new markers for prostate cancer"] Check |url= value (help). Ups. J. Med. Sci. 106 (1): 43–49. doi:10.3109/2000-1967-171. PMID 11817562.
  47. ↑ Utleg, Angelita G.; Yi, Eugene C.; Xie, Tao; Shannon, Paul; White, James T.; Goodlett, David R.; Hood, Leroy; Lin, Biaoyang (1 July 2003). [PM:12746840 "Proteomic analysis of human prostasomes"] Check |url= value (help). The Prostate. 56 (2): 150–161. doi:10.1002/pros.10255. PMID 12746840.
  48. ↑ Poliakov, Anton; Spilman, Michael; Dokland, Terje; Amling, Christopher L.; Mobley, James A. (1 February 2009). [PM:18819103 "Structural heterogeneity and protein composition of exosome-like vesicles (prostasomes) in human semen"] Check |url= value (help). The Prostate. 69 (2): 159–167. doi:10.1002/pros.20860. PMID 18819103.
  49. ↑ Ronquist, K. Göran; Ek, Bo; Morrell, Jane; Stavreus-Evers, Anneli; Ström Holst, Bodil; Humblot, Patrice; Ronquist, Gunnar; Larsson, Anders (October 2013). [PM:23707955 "Prostasomes from four different species are able to produce extracellular adenosine triphosphate (ATP)"] Check |url= value (help). Biochimica et Biophysica Acta (BBA) - General Subjects. 1830 (10): 4604–4610. doi:10.1016/j.bbagen.2013.05.019. PMID 23707955.
  50. ↑ Lwaleed, Bashir A.; Greenfield, Robert S.; Birch, Brian R.; Cooper, Alan J. (5 April 2005). [PM:15886798 "Does human semen contain a functional haemostatic system? A possible role for Tissue Factor Pathway Inhibitor in fertility through semen liquefaction"] Check |url= value (help). Thrombosis and Haemostasis. 93 (5): 847–852. doi:10.1160/TH04-09-0600. PMID 15886798.
  51. ↑ Babiker, Adil; Nilsson Ekdahl, Kristina; Nilsson, Bo; Ronquist, Gunnar (February 2007). [PM:17253194 "Prothrombotic Effects of Prostasomes Isolated from Prostatic Cancer Cell Lines and Seminal Plasma"] Check |url= value (help). Seminars in Thrombosis and Hemostasis. 33 (1): 080–086. doi:10.1055/s-2006-958466. PMID 17253194.
  52. ↑ Babiker, Adil A.; Hamad, Osama A.; Sanchez, Javier; Ronquist, Gunnar; Nilsson, Bo; Ekdahl, Kristina Nilsson (1 March 2007). [PM:17219380 "Prothrombotic effect of prostasomes of metastatic cell and seminal origin"] Check |url= value (help). The Prostate. 67 (4): 378–388. doi:10.1002/pros.20497. PMID 17219380.
  53. 1 2 Ronquist, K. Göran; Ronquist, Gunnar; Carlsson, Lena; Larsson, Anders (15 May 2009). [PM:19143024 "Human prostasomes contain chromosomal DNA"] Check |url= value (help). The Prostate. 69 (7): 737–743. doi:10.1002/pros.20921. PMID 19143024.
  54. ↑ Ronquist, Göran K.; Larsson, Anders; Stavreus-Evers, Anneli; Ronquist, Gunnar (1 December 2012). [PM:22539202 "Prostasomes are heterogeneous regarding size and appearance but affiliated to one DNA-containing exosome family"] Check |url= value (help). The Prostate. 72 (16): 1736–1745. doi:10.1002/pros.22526. PMID 22539202.
  55. ↑ Ronquist, Göran K.; Larsson, Anders; Ronquist, Gunnar; Isaksson, Anders; Hreinsson, Julius; Carlsson, Lena; Stavreus-Evers, Anneli (July 2011). [PM:21638509 "Prostasomal DNA characterization and transfer into human sperm"] Check |url= value (help). Molecular Reproduction and Development. 78 (7): 467–476. doi:10.1002/mrd.21327. PMID 21638509.
  56. ↑ Tavoosidana, G.; Ronquist, G.; Darmanis, S.; Yan, J.; Carlsson, L.; Wu, D.; Conze, T.; Ek, P.; Semjonow, A.; Eltze, E.; Larsson, A.; Landegren, U. D.; Kamali-Moghaddam, M. (9 May 2011). [PM:21555566 "Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer"] Check |url= value (help). Proceedings of the National Academy of Sciences. 108 (21): 8809–8814. doi:10.1073/pnas.1019330108. PMID 21555566.
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