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Exosomes are 50-90 nm vesicles secreted by a wide range of mammalian cell types.[1] First discovered in maturing mammalian reticulocytes, they were shown to be a mechanism for selective removal of many plasma membrane proteins.[2] 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.[3] For a list of exosome protein markers that are more often identified in exosomes, see ExoCarta, exosome database. 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.[4] Intralumenal endosomal vesicles can become exosomes in case they are released to the extracellular medium [5].

An exosome is created intracellularly when a segment of the cell membrane spontaneously invaginates and is endocytosed.[1] The internalized segment is broken into smaller vesicles that are subsequently expelled from the cell. The latter stage occurs when the late endosome, containing many small vesicles , fuses with the cell membrane, triggering the release of the vesicles from the cell. The vesicles (once released are called exosomes) consist of a lipid raft embedded with ligands common to the original cell membrane. Exosomes secreted by cells under normal and pathological conditions contain proteins and functional RNA molecules including mRNA and miRNA, which can be shuttled from one cell to another, affecting the recipient cell's protein production. This RNA is called "exosomal shuttle RNA".[6] An overview of molecules known to be present in exosomes is provided in the ExoCarta database.[7]

Clinical applications

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.[8]. Exosomes can also be released into urine by the kidneys and their detection might serve as a diagnostic tool.[9][10] Urinary exosomes may be useful as treatment response markers in prostate cancer.[11][12]

References

1. ^ a b 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. ^ 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.
3. ^ Mathivanan S, Lim JW, Tauro BJ, Ji H, Moritz RL, Simpson RJ (2009). "Proteomic 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. PMID 19837982.
4. ^ 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.
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.
6. ^ 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.
7. ^ Mathivanan, S.; Simpson, R (2009). "ExoCarta: A compendium of exosomal proteins and RNA.". Proteomics 9 (21): NA. doi:10.1002/pmic.200900351. PMID 19810033. http://www3.interscience.wiley.com/journal/122616918/abstract.
8. ^ 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.
9. ^ 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. PMID 15326289. PMC 516573. http://www.pnas.org/content/101/36/13368.full. Retrieved 2009-10-01.
10. ^ "Urinary Exosome Protein Database". NHLBI. 2009-05-12. http://dir.nhlbi.nih.gov/papers/lkem/exosome/. Retrieved 2009-10-01.
11. ^ "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.
12. ^ 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: 4. doi:10.1186/1479-5876-7-4. PMID 19138409. PMC 2631476. http://www.translational-medicine.com/content/7/1/4. Retrieved 2009-10-01.