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Exosome (vesicle)

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For other uses, see Exosome (disambiguation).

Exosomes are 30 to 90 nm vesicles secreted by a wide range of mammalian cell types.[1] It is larger than the LDL that has a size of 22 nm, but much smaller than a red blood cell, an erythrocyte, that is 6000 to 8000 nm in diameter and has a thickness of 2000 nm. Exosomes are released from the cell when multivesicular bodies fuse with the plasma membrane.[2]

Background

First discovered in the maturing mammalian reticulocyte (immature red blood cell), exosomes were shown to participate in selective removal of many plasma membrane proteins[3] as the reticulocyte becomes a mature red blood cell (erythrocyte). In the reticulocyte, as in most mammalian cells, portions of the plasma membrane are regularly internalized as endosomes, with 50 to 180% of the plasma membrane being recycled every hour.[4] In turn, parts of the membranes of some endosomes are subsequently internalized as smaller vesicles. Such endosomes are called multivesicular bodies because of their appearance, with many small vesicles, or "intralumenal endosomal vesicles," inside the larger body. The intralumenal endosomal vesicles become exosomes if the multivesicular body merges with the cell membrane, releasing the internal vesicles into the extracellular space.[5]

Exosomes contain various molecular constituents of their cell of origin, including proteins and RNA. Although the exosomal protein composition varies with the cell and tissue of origin, most exosomes contain an evolutionary-conserved common set of protein molecules. The RNA molecules in exosomes include mRNA and miRNA. One study suggested that miRNAs in exosomes secreted by mesenchymal stem cells (MSC) are predominantly pre- and not mature miRNAs.[6] Because the authors of this study did not find RNA-induced silencing complex-associated proteins in these exosomes, they suggested that only the pre-miRNAs but not the mature miRNAs in MSC exosomes have the potential to be biologically active in the recipient cells.

Scientists are actively researching the role that exosomes may play in cell-to-cell signaling, hypothesizing that because exosomes can merge with and release their contents into cells that are distant from their cell of origin, they may influence processes in the recipient cell. For example, RNA that is shuttled from one cell to another, known as "exosomal shuttle RNA," could potentially affect protein production in the recipient cell.[7][8] By transferring molecules from one cell to another, exosomes from certain cells of the immune system, such as dendritic cells and B cells, may play a functional role in mediating adaptive immune responses to pathogens and tumors.[9] Conversely, exosome production and content may be influenced by molecular signals received by the cell of origin. As evidence for this hypothesis, 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 favorable environment.[10] On the other hand, myc-immortalization of mesenchymal stem cell (MSC) did not alter the cardioprotective potency of its secreted exosomes.[11] Currently, there are no proven mechanisms by which microvesicles trigger intercellular communication. Possible mechanisms by which microvesicles trigger intercellular communication are paracrine, fusion and phagocytosis. [12]

Terminology

Exosomes are also referred to as microvesicles, epididimosomes, argosomes, exosome-like vesicles, microparticles, promininosomes, prostasomes, dexosomes, texosomes, dex, tex, archeosomes and oncosomes.[13] This confusion in terminology has led to typical exosome preparations sometimes being referred to as microvesicles and vice versa.

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.[14] Exosomes can also be released into urine by the kidneys, and their detection might serve as a diagnostic tool.[15][16][17] Urinary exosomes may be useful as treatment response markers in prostate cancer.[18][19] Exosomes released from tumors into the blood may also have diagnostic potential.

Databases

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

See also

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. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  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. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  4. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 21878991, please use {{cite journal}} with |pmid=21878991 instead.
  5. ^ 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. {{cite journal}}: Cite has empty unknown parameter: |author-name-separator= (help); More than one of |author1= and |last1= specified (help); More than one of |author2= and |last2= specified (help); Unknown parameter |author-separator= ignored (help)
  6. ^ 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.
  7. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1038/ncomms1180, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1038/ncomms1180 instead.
  8. ^ 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. {{cite journal}}: Cite has empty unknown parameter: |author-name-separator= (help); More than one of |author1= and |last1= specified (help); More than one of |author2= and |last2= specified (help); More than one of |author3= and |last3= specified (help); More than one of |author4= and |last4= specified (help); More than one of |author5= and |last5= specified (help); More than one of |author6= and |last6= specified (help); Unknown parameter |author-separator= ignored (help)
  9. ^ 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. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  10. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  11. ^ Chen, T.S.; Arslan, F.; Yin, Y.; Tan, S.S.; Lai, R.C.; Choo, A.; Padmanabhand, J.; Lee, C.N.; de Kleijn, D.P.V. (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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  12. ^ Mathivanan, S. Exosomes and Shedding Microvesicles are Mediators of Intercellular Communication: How do they Communicate with the Target Cells? (2012). J Biotechnol Biomater 2012, 2:6. Avalaible online
  13. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  14. ^ 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. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  15. ^ 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. Bibcode:2004PNAS..10113368P. doi:10.1073/pnas.0403453101. PMC 516573. PMID 15326289. Retrieved 2009-10-01.
  16. ^ "Urinary Exosome Protein Database". NHLBI. 2009-05-12. Retrieved 2009-10-01.
  17. ^ 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.
  18. ^ "Fat capsules carry markers for deadly prostate cancer". The Medical News. Retrieved 2009-10-01.
  19. ^ 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. Retrieved 2009-10-01. {{cite journal}}: More than one of |author= and |last1= specified (help)CS1 maint: unflagged free DOI (link)
  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.

External links

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