Exosome (vesicle)

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Exosomes are 30 to 90 nm vesicles secreted by a wide range of mammalian cell types.[1] They release contents outside of the cell after multivesicular bodies from endosomes fuse with the plasma membrane.[2]

Contents

[edit] Background

First discovered in maturing mammalian reticulocytes, they were shown to be a mechanism for selective removal of many plasma membrane proteins.[3] These proteins are lost or reduced in amount, without concomitant degradation, during the maturation to the erythrocyte. Although the exosomal protein composition varies with the cell of origin, most exosomes contain the soluble protein Hsc 70 and many others. 31 proteins are found to be in common between colorectal cancer, mast cells and urine-derived exosomes.[4] Certain cells of the immune system, such as dendritic cells and B cells, secrete exosomes that many scientists believe play a functional role in mediating adaptive immune responses to pathogens and tumors.[5] Intralumenal endosomal vesicles can become exosomes in case they are released to the extracellular medium.[6]

Exosomes contain both proteins and RNA molecules. Most exosomes studied to date have an evolutionary-conserved set of protein molecules and a set of tissue/cell type-specific proteins that distinguishes exosomes secreted by different cell types. Exosome protein cargo could also be modulated by the external microenvironment. For example, tumor cells exposed to hypoxia secrete exosomes with enhanced angiogenic and metastatic potential suggesting that tumor cells adapt to a hypoxic microenvironment by secreting exosomes to stimulate angiogenesis or facilitate metastasis to more favourable environment.[7] On the other hand, myc-immortalization of mesenchymal stem cell did not alter the cardioprotective potency of its secreted exosomes. [8] The RNA molecules in exosomes include mRNA and miRNA, which can be shuttled from one cell to another, affecting the recipient cell's protein production.[9] This RNA is called "exosomal shuttle RNA".[10] Many of the miRNAs in exosomes secreted by mesenchymal stem cells are predominantly pre- and not mature miRNAs.[11] There were no RISC-associated proteins in these exosomes, suggesting that only the pre-miRNAs but not the mature miRNAs in MSC exosomes have the potential to be biologically active in the recipient cells.

[edit] Terminology

Exosomes are also referred to as microvesicles, epididimosomes, argosomes, exosome-like vesicles, microparticles, promininosomes, prostasomes, dexosomes, texosomes, dex, tex, archeosomes and oncosomes.[12] This confusion in terminology has led to typical exosome preparations sometimes being referred to as microvesicles and vice versa.

[edit] Research

Exosomes from red blood cells contain the transferrin receptor which is absent in mature erythrocytes. Dendritic cell-derived exosomes express MHC I, MHC II, and costimulatory molecules and have been proven to be able to induce and enhance antigen-specific T cell responses in vivo. In addition, the first exosome-based cancer vaccination platforms are being explored in early clinical trials.[13] Exosomes can also be released into urine by the kidneys and their detection might serve as a diagnostic tool.[14][15][16] Urinary exosomes may be useful as treatment response markers in prostate cancer.[17][18] Exosomes released from tumors into the blood can also be used diagnostically. Exosomes carry RNA from the cell it was released from, and J. Skog, et al.[19] were the first[citation needed] to show that tumor mutations in brain tumors can be detected in exosomes from a serum sample, facilitating a blood-based biomarker platform for solid tumors.[citation needed]

[edit] Databases

An overview of molecules known to be present in exosomes is provided by the ExoCarta database.[20]

[edit] See also

[edit] References

  1. ^ Keller S, Sanderson MP, Stoeck A, Altevogt P (2006). "Exosomes: from biogenesis and secretion to biological function". Immunol. Lett. 107 (2): 102–8. doi:10.1016/j.imlet.2006.09.005. PMID 17067686. 
  2. ^ Exosomes MeSH. NCBI. Accessed February 15, 2011.
  3. ^ van Niel G, Porto-Carreiro I, Simoes S, Raposo G (2006). "Exosomes: a common pathway for a specialized function". J. Biochem. 140 (1): 13–21. doi:10.1093/jb/mvj128. PMID 16877764. 
  4. ^ Mathivanan S, Lim JW, Tauro BJ, Ji H, Moritz RL, Simpson J (2009). "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 9 (2): 197–208. doi:10.1074/mcp.M900152-MCP200. PMC 2830834. PMID 19837982. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2830834. 
  5. ^ Li XB, Zhang ZR, Schluesener HJ, Xu SQ (2006). "Role of exosomes in immune regulation". J. Cell. Mol. Med. 10 (2): 364–75. doi:10.1111/j.1582-4934.2006.tb00405.x. PMID 16796805. 
  6. ^ Gruenberg J, Van Der Goot FG (2006). "Mechanisms of pathogen entry through the endosomal compartments". Nature reviews 7 (7): 495–504. doi:10.1038/nrm1959. PMID 16773132. 
  7. ^ Park, J.E.; Tan, H.S.; Datta, A.; Lai, R.C.; Zhang, H.; Meng, W.; Lim, S.-K.; Sze, S.K. (2010). "Hypoxic Tumor Cell Modulates Its Microenvironment to Enhance Angiogenic and Metastatic Potential by Secretion of Proteins and Exosomes". Molecular and Cellular Proteomics 9 (6): 1085–99.. doi:10.1074/mcp.M900381-MCP200. PMC 2877972. PMID 20124223. http://www.mcponline.org/content/9/6/1085.full.pdf+html. 
  8. ^ Chen, T.S.; Arslan, F.; Yin, Y.; Tan, S.S.; Lai, R.C.; Choo, A.; Padmanabhand, J.; Lee, C.N. et al (2011). "Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs". Journal of Translational Medicine 9: 47.. doi:10.1186/1479-5876-9-47. PMC 3100248. PMID 21513579. http://www.translational-medicine.com/content/9/1/47. 
  9. ^ Balaj, L.; Lessard, R.; Dai, L.; Cho, Y. J.; Pomeroy, S. L.; Breakefield, X. O.; Skog, J. (2011). "Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences". Nature Communications 2 (2): 180. Bibcode 2011NatCo...2E.180B. doi:10.1038/ncomms1180. PMC 3040683. PMID 21285958. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3040683.  edit
  10. ^ Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (2007). "Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells". Nat. Cell Biol. 9 (6): 654–9. doi:10.1038/ncb1596. PMID 17486113. 
  11. ^ Chen, TS; Lai, RC; Lee, MM; Choo, AB; Lee, CN; Lim, SK (2010). "Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs". Nucleic Acids Res 38 (1): 215–224. doi:10.1093/nar/gkp857. PMC 2800221. PMID 19850715. http://nar.oxfordjournals.org/content/38/1/215.long. 
  12. ^ Simpson, RJ; Mathivanan, S (2012). "Extracellular Microvesicles: The Need for Internationally Recognised Nomenclature and Stringent Purification Criteria". J Proteomics Bioinform (2). doi:10.4172/jpb.10000e10. http://www.omicsonline.org/0974-276X/JPB-05-Editorial10.php?%20aid=4410. 
  13. ^ Mignot G, Roux S, Thery C, Ségura E, Zitvogel L (2006). "Prospects for exosomes in immunotherapy of cancer". J. Cell. Mol. Med. 10 (2): 376–88. doi:10.1111/j.1582-4934.2006.tb00406.x. PMID 16796806. 
  14. ^ Pisitkun, T; Shen, RF; Knepper, MA (2004). "Identification and proteomic profiling of exosomes in human urine". Proceedings of the National Academy of Sciences of the United States of America 101 (36): 13368–73. doi:10.1073/pnas.0403453101. PMC 516573. PMID 15326289. http://www.pnas.org/content/101/36/13368.full. Retrieved 2009-10-01. 
  15. ^ "Urinary Exosome Protein Database". NHLBI. 2009-05-12. http://dir.nhlbi.nih.gov/papers/lkem/exosome/. Retrieved 2009-10-01. 
  16. ^ Nilsson, J; Skog, J; Nordstrand, A; Baranov, V; Mincheva-Nilsson, L; Breakefield, XO; Widmark, A (2009). "Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer". British Journal of Cancer 100 (10): 1603–1607. doi:10.1038/sj.bjc.6605058. PMC 2696767. PMID 19401683. http://www.nature.com/bjc/journal/v100/n10/full/6605058a.html. 
  17. ^ "Fat capsules carry markers for deadly prostate cancer". The Medical News. http://www.news-medical.net/news/2009/05/12/Fat-capsules-carry-markers-for-deadly-prostate-cancer.aspx. Retrieved 2009-10-01. 
  18. ^ Mitchell, PJ; Welton, J; Staffurth, J; Court, J; Mason, MD; Tabi, Z; Clayton, A (2009). "Can urinary exosomes act as treatment response markers in prostate cancer?". J Transl Med. 7 (1): 4. doi:10.1186/1479-5876-7-4. PMC 2631476. PMID 19138409. http://www.translational-medicine.com/content/7/1/4. Retrieved 2009-10-01. 
  19. ^ Skog, Johan; Würdinger, Tom; van Rijn, Sjoerd; Meijer, Dimphna H; Gainche, Laura; Curry, Jr., William T; Carter, Bob S; Krichevsky, Anna M et al (2008). "Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers". Nature Cell Biology 10 (12): 1470–1476. doi:10.1038/ncb1800. PMID 19011622. http://www.nature.com/ncb/journal/v10/n12/full/ncb1800.html. 
  20. ^ Mathivanan, S.; Simpson, R (2009). "ExoCarta: A compendium of exosomal proteins and RNA". Proteomics 9 (21): 4997–5000. doi:10.1002/pmic.200900351. PMID 19810033. http://www3.interscience.wiley.com/journal/122616918/abstract. 

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