Prostasomes

Prostasomes are extracellular 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 lipid bilayer membrane, resembling that of lipid raft domains. Prostasomes appear to improve sperm motility and protect against attacks from the female immune defense during the passage to the egg.[2]

The name prostasomes was coined in the early 1980s by combining the terms "prosta"=prostate and "soma" (Greek for "body"). Around this time, the first functional studies of prostasomes were also performed.[3][4][5][6][7]

Cancerous prostate cells and prostate cells with low differentiation continue to produce and secrete prostasomes.[8] Possibly, the high incidence of prostate cancer in elderly men could be due to the immunomodulatory properties of prostasomes, protecting the cancer from attack by the immune system.

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).[9][10][11] Prostasomes also contain high levels of the divalent cations: Zn2+, Ca2+ and Mg2+.

Historical background of prostasome research
Year
1977-78An ATPase activity in seminal plasma indicated an occurrence of membrane-surrounded extracellular vesicles [12][13][14]
1981The first association between prostasomes and fertility was reported [15]
1983The 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]
1984The role of prostasomes in infertility and prostate cancer was investigated [18]
1986-89Studies on ATPases on the prostasomal surface [19][20][21][22]
1989The prostasomal membrane was found to have a much higher cholesterol/phospholipid ratio than ordinary cellular membranes [23]
1990Nucleic acid was found to be associated with prostasomes.[24] An interaction between prostasomes and sperm was shown [25]
1991-94Prostasomes and their role in immunosuppression were investigated in several articles.[26][27][28] Granulophysin (CD63) was suggested as a marker for prostasomes[29]
1995-2001Monoclonal antibodies against prostasomes were produced and several studies involving these antibodies were performed [30][31][32] as well as prostasome-sperm interaction studies.[33][34][35][36][37][38] Prostasomes were discovered in prostatic fluid of other species.[39][40] Prostatic cancer cell lines were found to produce prostasomes.[41][42] Prostasomes displayed anti-bacterial activity[43]
2001Autoantibodies against prostasomes were evaluated as biomarkers for prostate cancer [44]
2003The first comprehensive shotgun proteomics of the prostasome proteome [45] and it has been followed by two others [46][47]
2005Haemostasis coupled to prostasomes and the prostasomal membrane in fertility and in cancer [48][49][50]
2009-Investigation of prostasomal DNA.[51][52][53] DNA was found in both non-malignant prostasomes as well as in prostate cancer (PC3) cell derived prostasomes/exosomes [51]
2009-Prostasomes as a serum biomarker of prostate cancer [54]
2015Lipid rafts purified from prostasome membranes [55]

See also

References
  1. Ronquist G, Brody I (September 1985). "The prostasome: its secretion and function in man". Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes. 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". Human Reproduction Update. 12 (3): 283–92. doi:10.1093/humupd/dmi052. PMID 16373403.
  3. Stegmayr B, Brody I, Ronquist G (February 1982). "A biochemical and ultrastructural study on the endogenous protein kinase activity of secretory granule membranes of prostatic origin in human seminal plasma". Journal of Ultrastructure Research. 78 (2): 206–14. doi:10.1016/s0022-5320(82)80024-5. PMID 6283103.
  4. Stegmayr B, Ronquist G (1982). "Stimulation of sperm progressive motility by organelles in human seminal plasma". Scandinavian Journal of Urology and Nephrology. 16 (2): 85–90. doi:10.3109/00365598209179734. PMID 7123173.
  5. Stegmayr B, Ronquist G (1982). "Distribution of cyclic AMP in human seminal plasma and its relation to sperm progressive motility". Scandinavian Journal of Urology and Nephrology. 16 (2): 91–5. doi:10.3109/00365598209179735. PMID 6289426.
  6. Stegmayr B, Ronquist G (1982). "Promotive effect on human sperm progressive motility by prostasomes". Urological Research. 10 (5): 253–7. doi:10.1007/bf00255932. PMID 6219486.
  7. Stegmayr B, Berggren PO, Ronquist G, Hellman B (1982). "Calcium, magnesium, and zinc contents in organelles of prostatic origin in human seminal plasma". Scandinavian Journal of Urology and Nephrology. 16 (3): 199–203. doi:10.3109/00365598209179753. PMID 6219456.
  8. Ronquist G, Nilsson BO (2004). "The Janus-faced nature of prostasomes: their pluripotency favours the normal reproductive process and malignant prostate growth". Prostate Cancer and Prostatic Diseases. 7 (1): 21–31. doi:10.1038/sj.pcan.4500684. PMID 14999234.
  9. Ronquist G, Jin M, Schrimpf S, Nilsson BO (1997). "Prostasomes and human reproduction". In Motta PM (ed.). Microscopy of Reproduction and Development: A Dynamic Approach. Rome: Antonio Delfino Editore. pp. 213–219.
  10. Ronquist G, Carlsson L, Larsson A, Nilsson BO (2002). "Prostasomes". In Nilsson BO, Ronquist G (eds.). Prostasomes: proceedings from a symposium held at the Wenner-Gren Centre, Stockholm, in June 2001. London: Portland. pp. 1–9. ISBN 978-1-85578-151-1.
  11. Stewart AB, Anderson W, Delves G, Lwaleed BA, Birch B, Cooper A (November 2004). "Prostasomes: a role in prostatic disease?" (PDF). BJU International. 94 (7): 985–9. doi:10.1111/j.1464-410X.2004.05091.x. PMID 15541114.
  12. Ronquist G, Hedström M (August 1977). "Restoration of detergent-inactivated adenosine triphosphatase activity of human prostatic fluid with concanavalin A". Biochimica et Biophysica Acta (BBA) - Enzymology. 483 (2): 483–6. doi:10.1016/0005-2744(77)90078-x. PMID 142513.
  13. Ronquist G, Brody I, Gottfries A, Stegmayr B (1978). "An Mg2+ and Ca2+-stimulated adenosine triphosphatase in human prostatic fluid: part I". Andrologia. 10 (4): 261–72. doi:10.1111/j.1439-0272.1978.tb03030.x. PMID 152589.
  14. Ronquist G, Brody I, Gottfries A, Stegmayr B (1978). "An Mg2+ and Ca2+-stimulated adenosine triphosphatase in human prostatic fluid--part II". Andrologia. 10 (6): 427–33. doi:10.1111/j.1439-0272.1978.tb03064.x. PMID 153718.
  15. Brody I, Ronquist G, Gottfries A, Stegmayr B (1981). "Abnormal deficiency of both Mg2+ and Ca2+-dependent adenosine triphosphatase and secretory granules and vesicles in human seminal plasma". Scandinavian Journal of Urology and Nephrology. 15 (2): 85–90. doi:10.3109/00365598109179581. PMID 6120566.
  16. Ronquist G, Stegmayr B, Brody I, Gottfries A (March 1983). "[Prostasomes--a newly discovered organelle that increases sperm motility]". Lakartidningen. 80 (9): 810–3. PMID 6865591.
  17. Brody I, Ronquist G, Gottfries A (1983). "Ultrastructural localization of the prostasome - an organelle in human seminal plasma". Upsala Journal of Medical Sciences. 88 (2): 63–80. doi:10.3109/03009738309178440. PMID 6649193.
  18. Ronquist G, Stegmayr B (1984). "Prostatic origin of fucosyl transferase in human seminal plasma--a study on healthy controls and on men with infertility or with prostatic cancer". Urological Research. 12 (5): 243–7. doi:10.1007/bf00256148. PMID 6240149.
  19. Ronquist G, Frithz GG (1986). "Prostasomes in human semen contain ADP and GDP". Acta Europaea Fertilitatis. 17 (4): 273–6. PMID 3577591.
  20. Ronquist G (June 1987). "Effect of modulators on prostasome membrane-bound ATPase in human seminal plasma". European Journal of Clinical Investigation. 17 (3): 231–6. doi:10.1111/j.1365-2362.1987.tb01241.x. PMID 2957209.
  21. Ronquist G (1988). "Zinc ion stimulation of ATP cleavage by prostasomes from human seminal plasma". Urologia Internationalis. 43 (6): 334–40. doi:10.1159/000281386. PMID 2977004.
  22. Ronquist G, Frithz G, Jansson A (1988). "Prostasome membrane associated enzyme activities and semen parameters in men attending an infertility clinic". Urologia Internationalis. 43 (3): 133–8. doi:10.1159/000281325. PMID 2902707.
  23. Arvidson G, Ronquist G, Wikander G, Ojteg AC (September 1989). "Human prostasome membranes exhibit very high cholesterol/phospholipid ratios yielding high molecular ordering". Biochimica et Biophysica Acta (BBA) - Biomembranes. 984 (2): 167–73. doi:10.1016/0005-2736(89)90212-5. PMID 2548623.
  24. Olsson I, Ronquist G (1990). "Nucleic acid association to human prostasomes". Archives of Andrology. 24 (1): 1–10. doi:10.3109/01485019008986852. PMID 1691619.
  25. Ronquist G, Nilsson BO, Hjertën S (1990). "Interaction between prostasomes and spermatozoa from human semen". Archives of Andrology. 24 (2): 147–57. doi:10.3109/01485019008986874. PMID 2327824.
  26. Kelly RW, Holland P, Skibinski G, Harrison C, McMillan L, Hargreave T, James K (December 1991). "Extracellular organelles (prostasomes) are immunosuppressive components of human semen". Clinical and Experimental Immunology. 86 (3): 550–6. doi:10.1111/j.1365-2249.1991.tb02968.x. PMC 1554200. PMID 1747961.
  27. Skibinski G, Kelly RW, Harkiss D, James K (September 1992). "Immunosuppression by human seminal plasma--extracellular organelles (prostasomes) modulate activity of phagocytic cells". American Journal of Reproductive Immunology. 28 (2): 97–103. doi:10.1111/j.1600-0897.1992.tb00767.x. PMID 1337434.
  28. Rooney IA, Atkinson JP, Krul ES, Schonfeld G, Polakoski K, Saffitz JE, Morgan BP (May 1993). "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". The Journal of Experimental Medicine. 177 (5): 1409–20. doi:10.1084/jem.177.5.1409. PMC 2191001. PMID 7683035.
  29. Skibinski G, Kelly RW, James K (April 1994). "Expression of a common secretory granule specific protein as a marker for the extracellular organelles (prostasomes) in human semen". Fertility and Sterility. 61 (4): 755–9. doi:10.1016/s0015-0282(16)56658-8. PMID 8150122.
  30. Ronquist G, Fabiani R, Jin M, Nilsson BO, Elenbring K, Hjerten S (1996). "Adherence of human prostasomes to mouse spermatozoa and their displacement by monoclonal antibodies as revealed by free zone electrophoresis". Archives of Andrology. 36 (2): 101–7. doi:10.3109/01485019608987085. PMID 8907670.
  31. Nilsson BO, Jin M, Ronquist G (1996). "Immunolocalization of prostasomes in the human prostate". Upsala Journal of Medical Sciences. 101 (2): 149–57. doi:10.3109/03009739609178919. PMID 8897705.
  32. Nilsson BO, Jin M, Einarsson B, Persson BE, Ronquist G (May 1998). "Monoclonal antibodies against human prostasomes". The Prostate. 35 (3): 178–84. doi:10.1002/(SICI)1097-0045(19980515)35:3<178::AID-PROS3>3.0.CO;2-D. PMID 9582086.
  33. Arienti G, Carlini E, Verdacchi R, Cosmi EV, Palmerini CA (October 1997). "Prostasome to sperm transfer of CD13/aminopeptidase N (EC 3.4.11.2)". Biochimica et Biophysica Acta (BBA) - General Subjects. 1336 (3): 533–8. doi:10.1016/s0304-4165(97)00071-8. PMID 9367181.
  34. Arienti G, Carlini E, Verdacchi R, Palmerini CA (August 1997). "Transfer of aminopeptidase activity from prostasomes to sperm". Biochimica et Biophysica Acta (BBA) - General Subjects. 1336 (2): 269–74. doi:10.1016/S0304-4165(97)00036-6. PMID 9305799.
  35. Carlini E, Palmerini CA, Cosmi EV, Arienti G (July 1997). "Fusion of sperm with prostasomes: effects on membrane fluidity". Archives of Biochemistry and Biophysics. 343 (1): 6–12. doi:10.1006/abbi.1997.9999. PMID 9210640.
  36. Arienti G, Polci A, Carlini E, Palmerini CA (June 1997). "Transfer of CD26/dipeptidyl peptidase IV (E.C. 3.5.4.4) from prostasomes to sperm". FEBS Letters. 410 (2–3): 343–6. doi:10.1016/S0014-5793(97)00655-8. PMID 9237659.
  37. Arienti G, Carlini E, Palmerini CA (January 1997). "Fusion of human sperm to prostasomes at acidic pH". The Journal of Membrane Biology. 155 (1): 89–94. doi:10.1007/s002329900160. PMID 9002427.
  38. Renneberg H, Konrad L, Dammshäuser I, Seitz J, Aumüller G (February 1997). "Immunohistochemistry of prostasomes from human semen". 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.
  39. Arienti G, Carlini E, De Cosmo AM, Di Profio P, Palmerini CA (August 1998). "Prostasome-like particles in stallion semen". Biology of Reproduction. 59 (2): 309–13. doi:10.1095/biolreprod59.2.309. PMID 9687300.
  40. Minelli A, Moroni M, Martínez E, Mezzasoma I, Ronquist G (November 1998). "Occurrence of prostasome-like membrane vesicles in equine seminal plasma". Journal of Reproduction and Fertility. 114 (2): 237–43. doi:10.1530/jrf.0.1140237. PMID 10070353.
  41. Nilsson BO, Lennartsson L, Carlsson L, Nilsson S, Ronquist G (1999). "Expression of prostasome-like granules by the prostate cancer cell lines PC3, Du145 and LnCaP grown in monolayer". Upsala Journal of Medical Sciences. 104 (3): 199–206. doi:10.3109/03009739909178963. PMID 10680953.
  42. Nilsson BO, Egevad L, Jin M, Ronquist G, Busch C (April 1999). "Distribution of prostasomes in neoplastic epithelial prostate cells". 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.
  43. Carlsson L, Påhlson C, Bergquist M, Ronquist G, Stridsberg M (September 2000). "Antibacterial activity of human prostasomes". The Prostate. 44 (4): 279–86. doi:10.1002/1097-0045(20000901)44:4<279::AID-PROS4>3.0.CO;2-2. PMID 10951492.
  44. Nilsson BO, Carlsson L, Larsson A, Ronquist G (2001). "Autoantibodies to prostasomes as new markers for prostate cancer". Upsala Journal of Medical Sciences. 106 (1): 43–9. doi:10.3109/2000-1967-171. PMID 11817562.
  45. Utleg AG, Yi EC, Xie T, Shannon P, White JT, Goodlett DR, Hood L, Lin B (July 2003). "Proteomic analysis of human prostasomes". The Prostate. 56 (2): 150–61. doi:10.1002/pros.10255. PMID 12746840.
  46. Poliakov A, Spilman M, Dokland T, Amling CL, Mobley JA (February 2009). "Structural heterogeneity and protein composition of exosome-like vesicles (prostasomes) in human semen". The Prostate. 69 (2): 159–67. doi:10.1002/pros.20860. PMID 18819103.
  47. Ronquist KG, Ek B, Morrell J, Stavreus-Evers A, Ström Holst B, Humblot P, Ronquist G, Larsson A (October 2013). "Prostasomes from four different species are able to produce extracellular adenosine triphosphate (ATP)". Biochimica et Biophysica Acta (BBA) - General Subjects. 1830 (10): 4604–10. doi:10.1016/j.bbagen.2013.05.019. PMID 23707955.
  48. Lwaleed BA, Greenfield RS, Birch BR, Cooper AJ (May 2005). "Does human semen contain a functional haemostatic system? A possible role for Tissue Factor Pathway Inhibitor in fertility through semen liquefaction". Thrombosis and Haemostasis. 93 (5): 847–52. doi:10.1160/TH04-09-0600. PMID 15886798.
  49. Babiker AA, Ekdahl KN, Nilsson B, Ronquist G (February 2007). "Prothrombotic effects of prostasomes isolated from prostatic cancer cell lines and seminal plasma". Seminars in Thrombosis and Hemostasis. 33 (1): 80–6. doi:10.1055/s-2006-958466. PMID 17253194.
  50. Babiker AA, Hamad OA, Sanchez J, Ronquist G, Nilsson B, Ekdahl KN (March 2007). "Prothrombotic effect of prostasomes of metastatic cell and seminal origin". The Prostate. 67 (4): 378–88. doi:10.1002/pros.20497. PMID 17219380.
  51. Ronquist KG, Ronquist G, Carlsson L, Larsson A (May 2009). "Human prostasomes contain chromosomal DNA". The Prostate. 69 (7): 737–43. doi:10.1002/pros.20921. PMID 19143024.
  52. Ronquist GK, Larsson A, Stavreus-Evers A, Ronquist G (December 2012). "Prostasomes are heterogeneous regarding size and appearance but affiliated to one DNA-containing exosome family". The Prostate. 72 (16): 1736–45. doi:10.1002/pros.22526. PMID 22539202.
  53. Ronquist GK, Larsson A, Ronquist G, Isaksson A, Hreinsson J, Carlsson L, Stavreus-Evers A (July 2011). "Prostasomal DNA characterization and transfer into human sperm". Molecular Reproduction and Development. 78 (7): 467–76. doi:10.1002/mrd.21327. PMID 21638509.
  54. Tavoosidana G, Ronquist G, Darmanis S, Yan J, Carlsson L, Wu D, Conze T, Ek P, Semjonow A, Eltze E, Larsson A, Landegren UD, Kamali-Moghaddam M (May 2011). "Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer". Proceedings of the National Academy of Sciences of the United States of America. 108 (21): 8809–14. doi:10.1073/pnas.1019330108. PMC 3102389. PMID 21555566.
  55. Dubois L, Ronquist KK, Ek B, Ronquist G, Larsson A (November 2015). "Proteomic Profiling of Detergent Resistant Membranes (Lipid Rafts) of Prostasomes". Molecular & Cellular Proteomics. 14 (11): 3015–22. doi:10.1074/mcp.M114.047530. PMC 4638043. PMID 26272980.
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