Abstract
Exosomes are 30-120nm long endocytic membrane-derived vesicles, which are secreted by various types of cells and stably present in body fluids, such as plasma, urine, saliva and breast milk. Exosomes participate in intercellular communication. Recently accumulative studies have suggested that exosomes may serve as novel biomarkers for disease diagnosis and prognosis. Herein, we reviewed the biological features of exosomes, technologies for exosome isolation and identification, as well as progress in exosomal biomarker identification, highlighting the relevance of exosome to human diseases and significance and great potential in translational medicine.
Keywords: Exosome, Isolation, Biomarker, Protein, RNA, Diagnosis.
[1]
Trams EG, Lauter CJ, Salem NJ, et al. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta 1981; 645: 63-70.
[2]
Johnstone RM, Adam M, Hammond JR, et al. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem 1987; 262: 9412-20.
[3]
Dhondt B, Rousseau Q, De Wever O, et al. Function of extracellular vesicle-associated miRNAs in metastasis. Cell Tissue Res 2016; 365: 621-41.
[4]
Park JE, Tan HS, Datta A, et al. Hypoxic tumor cell modulates its microenvironment to enhance angiogenic and metastatic potential by secretion of proteins and exosomes. Mol Cell Proteomics 2010; 9: 1085-99.
[5]
Mathivanan S, Fahner CJ, Reid GE, et al. ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic Acids Res 2012; 40: D1241-4.
[6]
Conde-Vancells J, Rodriguez-Suarez E, Embade N, et al. Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res 2008; 7: 5157-66.
[7]
Yamashita T, Takahashi Y, Nishikawa M, et al. Effect of exosome isolation methods on physicochemical properties of exosomes and clearance of exosomes from the blood circulation. Eur J Pharm Biopharm 2016; 98: 1-8.
[8]
Ratajczak J, Wysoczynski M, Hayek F, et al. Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia 2006; 20: 1487-95.
[9]
Turchinovich A, Weiz L, Burwinkel B. Extracellular miRNAs: the mystery of their origin and function. Trends Biochem Sci 2012; 37: 460-5.
[10]
Miska EA. How microRNAs control cell division, differentiation and death. Curr Opin Genet Dev 2005; 15: 563-8.
[11]
Feng DQ, Huang B, Li J, et al. Selective miRNA expression profile in chronic myeloid leukemia K562 cell-derived exosomes. Asian Pac J Cancer Prev 2013; 14: 7501-8.
[12]
Record M, Carayon K, Poirot M, et al. Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies. Biochim Biophys Acta 2014; 1841: 108-20.
[13]
Valadi H, Ekstrom K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9: 654-9.
[14]
Thakur BK, Zhang H, Becker A, et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res 2014; 24: 766-9.
[15]
Zakharova L, Svetlova M, Fomina AF. T cell exosomes induce cholesterol accumulation in human monocytes via phosphatidylserine receptor. J Cell Physiol 2007; 212: 174-81.
[16]
Hong BS, Cho JH, Kim H, et al. Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells. BMC Genomics 2009; 10: 556.
[17]
Thery C, Amigorena S, Raposo G, et al. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol . 2006. Chapter 3:
Unit 3.22.
[18]
Van Niel G, Mallegol J, Bevilacqua C, et al. Intestinal epithelial exosomes carry MHC class II/peptides able to inform the immune system in mice. Gut 2003; 52: 1690-7.
[19]
Muller L, Hong CS, Stolz DB, et al. Isolation of biologically-active exosomes from human plasma. J Immunol Methods 2014; 411: 55-65.
[20]
Thery C, Amigorena S, Raposo G, et al. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol. 2006. Chapter 3:
Unit 3.22.
[21]
Momen-Heravi F, Balaj L, Alian S, et al. Impact of biofluid viscosity on size and sedimentation efficiency of the isolated microvesicles. Front Physiol 2012; 3: 162.
[22]
Lamparski HG, Metha-Damani A, Yao JY, et al. Production and characterization of clinical grade exosomes derived from dendritic cells. J Immunol Methods 2002; 270: 211-26.
[23]
Raposo G, Nijman HW, Stoorvogel W, et al. B lymphocytes secrete antigen-presenting vesicles. J Exp Med 1996; 183: 1161-72.
[24]
Greening DW, Xu R, Ji H, et al. A protocol for exosome isolation and characterization: evaluation of ultra-centrifugation, density-gradient separation, and immuno-affinity capture methods. Methods Mol Biol 2015; 1295: 179-209.
[25]
Rider MA, Hurwitz SN, Meckes DJ. ExtraPEG: A Polyethylene Glycol-Based Method for Enrichment of Extracellular Vesicles. Sci Rep 2016; 6: 23978.
[26]
Li P, Kaslan M, Lee SH, et al. Progress in Exosome Isolation Techniques. Theranostics 2017; 7: 789-804.
[27]
Lai RC, Arslan F, Lee MM, et al. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res 2010; 4: 214-22.
[28]
Cheruvanky A, Zhou H, Pisitkun T, et al. Rapid isolation of urinary exosomal biomarkers using a nanomembrane ultrafiltration concentrator. Am J Physiol Renal Physiol 2007; 292: F1657-61.
[29]
Clayton A, Court J, Navabi H, et al. Analysis of antigen presenting cell derived exosomes, based on immuno-magnetic isolation and flow cytometry. J Immunol Methods 2001; 247: 163-74.
[30]
Nakai W, Yoshida T, Diez D, et al. A novel affinity-based method for the isolation of highly purified extracellular vesicles. Sci Rep 2016; 6: 33935.
[31]
Zarovni N, Corrado A, Guazzi P, et al. Integrated isolation and quantitative analysis of exosome shuttled proteins and nucleic acids using immunocapture approaches. Methods 2015; 87: 46-58.
[32]
Liga A, Vliegenthart AD, Oosthuyzen W, et al. Exosome isolation: a microfluidic road-map. Lab Chip 2015; 15: 2388-94.
[33]
Lotvall J, Hill AF, Hochberg F, et al. Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J Extracell Vesicles 2014; 3: 26913.
[34]
Witwer KW, Buzas EI, Bemis LT, et al. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles 2013; 2(1): 20360.
[35]
Zonneveld MI, Brisson AR, van Herwijnen MJ, et al. Recovery of extracellular vesicles from human breast milk is influenced by sample collection and vesicle isolation procedures. J Extracell Vesicles 2014; 3(1): 24215.
[36]
Huynh N, VonMoss L, Smith D, et al. Characterization of regulatory extracellular vesicles from osteoclasts. J Dent Res 2016; 95: 673-9.
[37]
Morhayim J, van de Peppel J, Demmers JA, et al. Proteomic signatures of extracellular vesicles secreted by nonmineralizing and mineralizing human osteoblasts and stimulation of tumor cell growth. FASEB J 2015; 29: 274-85.
[38]
Melo SA, Luecke LB, Kahlert C, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 2015; 523: 177-82.
[39]
Logozzi M, De Milito A, Lugini L, et al. High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients. PLoS One 2009; 4e5219
[40]
Yoshioka Y, Konishi Y, Kosaka N, et al. Comparative marker analysis of extracellular vesicles in different human cancer types. J Extracell Vesicles 2013; 2.
[41]
Chen CL, Lai YF, Tang P, et al. Comparative and targeted proteomic analyses of urinary microparticles from bladder cancer and hernia patients. J Proteome Res 2012; 11: 5611-29.
[42]
Foglio E, Puddighinu G, Fasanaro P, et al. Exosomal clusterin, identified in the pericardial fluid, improves myocardial performance following MI through epicardial activation, enhanced arteriogenesis and reduced apoptosis. Int J Cardiol 2015; 197: 333-47.
[43]
Niu C, Wang X, Zhao M, et al. Macrophage Foam Cell-Derived Extracellular Vesicles Promote Vascular Smooth Muscle Cell Migration and Adhesion. J Am Heart Assoc 2016; 5(10)e004099
[44]
Goetzl EJ, Schwartz JB, Mustapic M, et al. Altered cargo proteins of human plasma endothelial cell-derived exosomes in atherosclerotic cerebrovascular disease. FASEB J 2017; 31: 3689-94.
[45]
Zhou H, Cheruvanky A, Hu X, et al. Urinary exosomal transcription factors, a new class of biomarkers for renal disease. Kidney Int 2008; 74: 613-21.
[46]
Welker MW, Reichert D, Susser S, et al. Soluble serum CD81 is elevated in patients with chronic hepatitis C and correlates with alanine aminotransferase serum activity. PLoS One 2012; 7e30796
[47]
Kruh-Garcia NA, Wolfe LM, Chaisson LH, et al. Detection of Mycobacterium tuberculosis peptides in the exosomes of patients with active and latent M. tuberculosis infection using MRM-MS. PLoS One 2014; 9e103811
[48]
Moon PG, Lee JE, Cho YE, et al. Identification of Developmental Endothelial Locus-1 on Circulating Extracellular Vesicles as a Novel Biomarker for Early Breast Cancer Detection. Clin Cancer Res 2016; 22: 1757-66.
[49]
Soki FN, Koh AJ, Jones JD, et al. Polarization of prostate cancer-associated macrophages is induced by milk fat globule-EGF factor 8 (MFG-E8)-mediated efferocytosis. J Biol Chem 2014; 289: 24560-72.
[50]
Conde-Vancells J, Rodriguez-Suarez E, Gonzalez E, et al. Candidate biomarkers in exosome-like vesicles purified from rat and mouse urine samples. Proteomics Clin Appl 2010; 4: 416-25.
[51]
Bijnsdorp IV, Geldof AA, Lavaei M, et al. Exosomal ITGA3 interferes with non-cancerous prostate cell functions and is increased in urine exosomes of metastatic prostate cancer patients. J Extracell Vesicles 2013; 2(1): 22097.
[52]
Khan S, Jutzy JM, Valenzuela MM, et al. Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer. PLoS One 2012; 7e46737
[53]
Yamashita T, Kamada H, Kanasaki S, et al. Epidermal growth factor receptor localized to exosome membranes as a possible biomarker for lung cancer diagnosis. Pharmazie 2013; 68: 969-73.
[54]
Tan KH, Tan SS, Sze SK, et al. Plasma biomarker discovery in preeclampsia using a novel differential isolation technology for circulating extracellular vesicles. Am J Obstet Gynecol 2014; 211: 380.e1-13..
[55]
Saraswat M, Joenvaara S, Musante L, et al. N-linked (N-) Glycoproteomics of Urinary Exosomes. Mol Cell Proteomics 2015; 14: 2298.
[56]
Lau KS, Partridge EA, Grigorian A, et al. Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell 2007; 129: 123-34.
[57]
Guo J, Cui Y, Yan Z, et al. Phosphoproteome characterization of human colorectal cancer SW620 cell-derived exosomes and new phosphosite discovery for C-HPP. J Proteome Res 2016; 15: 4060-72.
[58]
Lv LL, Cao YH, Pan MM, et al. CD2AP mRNA in urinary exosome as biomarker of kidney disease. Clin Chim Acta 2014; 428: 26-31.
[59]
Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008; 105: 10513-8.
[60]
Li D, Liu J, Guo B, et al. Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation. Nat Commun 2016; 7: 10872.
[61]
Iorio MV, Visone R, Di Leva G, et al. MicroRNA signatures in human ovarian cancer. Cancer Res 2007; 67: 8699-707.
[62]
Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 2008; 110: 13-21.
[63]
Ohshima K, Inoue K, Fujiwara A, et al. Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PLoS One 2010; 5e13247
[64]
Kuwabara Y, Ono K, Horie T, et al. Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage. Circ Cardiovasc Genet 2011; 4: 446-54.
[65]
Lv LL, Cao YH, Pan MM, et al. CD2AP mRNA in urinary exosome as biomarker of kidney disease. Clin Chim Acta 2014; 428: 26-31.
[66]
Rabinowits G, Gercel-Taylor C, Day JM, et al. Exosomal microRNA: a diagnostic marker for lung cancer. Clin Lung Cancer 2009; 10: 42-6.
[67]
Silva J, Garcia V, Zaballos A, et al. Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival. Eur Respir J 2011; 37: 617-23.
[68]
Brase JC, Johannes M, Schlomm T, et al. Circulating miRNAs are correlated with tumor progression in prostate cancer. Int J Cancer 2011; 28: 608-16.
[69]
Corcoran C, Friel AM, Duffy MJ, et al. Intracellular and extracellular microRNAs in breast cancer. Clin Chem 2011; 57: 18-32.
[70]
Chen JF, Mandel EM, Thomson JM, et al. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 2006; 38: 228-33.
[71]
Xu H, Dong X, Chen Y, et al. Serum exosomal hnRNPH1 mRNA as a novel marker for hepatocellular carcinoma. Clin Chem Lab Med 2018; 56: 479-84.
[72]
Lv LL, Cao YH, Ni HF, et al. MicroRNA-29c in urinary exosome/microvesicle as a biomarker of renal fibrosis. Am J Physiol Renal Physiol 2013; 305: F1220-7.
[73]
Nilsson J, Skog J, Nordstrand A, et al. Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer. Br J Cancer 2009; 100: 1603-7.
[74]
Palanisamy V, Sharma S, Deshpande A, et al. Nanostructural and transcriptomic analyses of human saliva derived exosomes. PLoS One 2010; 5e8577
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