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Translational Opportunities of Extracellular Vesicles in Biomedicine

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Circulating Tumor Cells

Part of the book series: Current Cancer Research ((CUCR))

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Abstract

Extracellular vesicles are nanoscaled particles continuously released by cells, reflecting their phenotype in their membrane and within their load. With each of its subsets (microvesicles, apoptotic bodies, exosomes), they have opened a highway for the study of intercellular communication mechanisms. However, their significant quantity and availability across myriad biofluids, as well as their cargo’s stability, are advantages these diverse vesicles have as circulating markers. While we unravel their dynamics, our technologies to analyze them have evolved. In this review, we will detail extracellular vesicles, their subtypes, and biogenesis. We will overview methods for their isolation and representative analysis platforms, both for their physical characterization and for their cargo assays (protein, nucleic acids, lipids). We will also comment on their potential translation as cancer biomarkers, fundamental research challenges, and their comparison with other circulating markers.

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References

  1. Houali K, Wang X, Shimizu Y, Djennaoui D, Nicholls J, Fiorini S, Bouguermouh A, Ooka T (2007) A New Diagnostic Marker for Secreted Epstein-Barr Virus–Encoded LMP1 and BARF1 Oncoproteins in the Serum and Saliva of Patients with Nasopharyngeal Carcinoma. Clinical Cancer Research 13:4993

    Article  CAS  PubMed  Google Scholar 

  2. Pisitkun T, Shen RF, Knepper MA (2004) Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci U S A 101:13368–13373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Perkumas KM, Hoffman EA, McKay BS, Allingham RR, Stamer WD (2007) Myocilin-associated exosomes in human ocular samples. Exp Eye Res 84:209–212

    Article  CAS  PubMed  Google Scholar 

  4. Bachy I, Kozyraki R, Wassef M (2008) The particles of the embryonic cerebrospinal fluid: how could they influence brain development. Brain Res Bull 75:289–294

    Article  CAS  PubMed  Google Scholar 

  5. Keller S, Rupp C, Stoeck A, Runz S, Fogel M, Lugert S, Hager HD, Abdel-Bakky MS, Gutwein P, Altevogt P (2007) CD24 is a marker of exosomes secreted into urine and amniotic fluid. Kidney Int 72:1095–1102

    Article  CAS  PubMed  Google Scholar 

  6. Andre F, Schartz NEC, Movassagh M, Flament C, Pautier P, Morice P, Pomel C, Lhomme C, Escudier B, Le Chevalier T, Tursz T, Amigorena S, Raposo G, Angevin E, Zitvogel L (2002) Malignant effusions and immunogenic tumour-derived exosomes. The Lancet 360:295–305

    Article  CAS  Google Scholar 

  7. Hood JL (2017) The association of exosomes with lymph nodes. Seminars in Cell and Developmental Biology 67:29–38

    Article  CAS  PubMed  Google Scholar 

  8. Admyre C, Grunewald J, Thyberg J, Gripenbäck S, Tornling G, Eklund A, Scheynius A, Gabrielsson S (2003) Exosomes with major histocompatibility complex class II and co-stimulatory molecules are present in human BAL fluid. Eur Respir J 22:578–583

    Article  CAS  PubMed  Google Scholar 

  9. Domenis R, Zanutel R, Caponnetto F, Toffoletto B, Cifù A, Pistis C, Di Benedetto P, Causero A, Pozzi M, Bassini F, Fabris M, Niazi KR, Soon-Shiong P, Curcio F (2017) Characterization of the Proinflammatory Profile of Synovial Fluid-Derived Exosomes of Patients with Osteoarthritis. Mediators Inflamm 2017:4814987

    Article  PubMed  PubMed Central  Google Scholar 

  10. Poliakov A, Spilman M, Dokland T, Amling CL, Mobley JA (2009) Structural heterogeneity and protein composition of exosome-like vesicles (prostasomes) in human semen. Prostate 69:159–167

    Article  PubMed  Google Scholar 

  11. Admyre C, Johansson SM, Qazi KR, Filén J-J, Lahesmaa R, Norman M, Neve EPA, Scheynius A, Gabrielsson S (2007) Exosomes with Immune Modulatory Features Are Present in Human Breast Milk. The Journal of Immunology 179:1969

    Article  CAS  PubMed  Google Scholar 

  12. Geeurickx E, Hendrix A (2020) Targets, pitfalls and reference materials for liquid biopsy tests in cancer diagnostics. Molecular Aspects of Medicine 72:100828

    Article  CAS  PubMed  Google Scholar 

  13. Tutrone R, Donovan MJ, Torkler P, Tadigotla V, McLain T, Noerholm M, Skog J, McKiernan J (2020) Clinical utility of the exosome based ExoDx Prostate(IntelliScore) EPI test in men presenting for initial Biopsy with a PSA 2-10 ng/mL. Prostate Cancer Prostatic Dis 23:607-614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yoshioka Y, Kosaka N, Konishi Y, Ohta H, Okamoto H, Sonoda H, Nonaka R, Yamamoto H, Ishii H, Mori M, Furuta K, Nakajima T, Hayashi H, Sugisaki H, Higashimoto H, Kato T, Takeshita F, Ochiya T (2014) Ultra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen. Nature Communications 5:3591

    Article  PubMed  Google Scholar 

  15. ** X, Chen Y, Chen H, Fei S, Chen D, Cai X, Liu L, Lin B, Su H, Zhao L, Su M, Pan H, Shen L, **e D, **e C (2017) Evaluation of Tumor-Derived Exosomal miRNA as Potential Diagnostic Biomarkers for Early-Stage Non-Small Cell Lung Cancer Using Next-Generation Sequencing. Clin Cancer Res 23:5311–5319

    Article  CAS  PubMed  Google Scholar 

  16. Mjelle R, Dima SO, Bacalbasa N, Chawla K, Sorop A, Cucu D, Herlea V, Sætrom P, Popescu I (2019) Comprehensive transcriptomic analyses of tissue, serum, and serum exosomes from hepatocellular carcinoma patients. BMC Cancer 19:1007

    Article  PubMed  PubMed Central  Google Scholar 

  17. Chargaff E, West R (1946) The biological significance of the thromboplastic protein of blood. J Biol Chem 166:189–197

    Article  CAS  PubMed  Google Scholar 

  18. Hargett LA, Bauer NN (2013) On the origin of microparticles: From “platelet dust” to mediators of intercellular communication. Pulmonary circulation 3:329–340

    Article  PubMed  PubMed Central  Google Scholar 

  19. Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C (1987) Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem 262:9412–9420

    Article  CAS  PubMed  Google Scholar 

  20. Théry C, Witwer KW, Aikawa E et al. (2018) Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. Journal of extracellular vesicles 7:1535750

    Article  PubMed  PubMed Central  Google Scholar 

  21. Mathieu M, Martin-Jaular L, Lavieu G, Théry C (2019) Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nature Cell Biology 21:9–17

    Article  CAS  PubMed  Google Scholar 

  22. Clotilde T, Laurence Z, Sebastian A (2002) Exosomes: composition, biogenesis and function. Nature Reviews Immunology 2:569

    Article  Google Scholar 

  23. Singhto N, Vinaiphat A, Thongboonkerd V (2019) Discrimination of urinary exosomes from microvesicles by lipidomics using thin layer liquid chromatography (TLC) coupled with MALDI-TOF mass spectrometry. Scientific Reports 9:13834

    Article  PubMed  PubMed Central  Google Scholar 

  24. Sanderson RD, Bandari SK, Vlodavsky I (2019) Proteases and glycosidases on the surface of exosomes: Newly discovered mechanisms for extracellular remodeling. Matrix Biology 75-76:160–169

    Article  CAS  PubMed  Google Scholar 

  25. Turchinovich A, Drapkina O, Tonevitsky A (2019) Transcriptome of Extracellular Vesicles: State-of-the-Art. Front Immunol 10:202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gregory CD, Dransfield I (2018) Apoptotic Tumor Cell-Derived Extracellular Vesicles as Important Regulators of the Onco-Regenerative Niche. Front Immunol 9:1111

    Article  PubMed  PubMed Central  Google Scholar 

  27. Pap E, Pállinger E, Pásztói M, Falus A (2009) Highlights of a new type of intercellular communication: microvesicle-based information transfer. Inflamm Res 58:1–8

    Article  CAS  PubMed  Google Scholar 

  28. Jurj A, Zanoaga O, Braicu C, Lazar V, Tomuleasa C, Irimie A, Berindan-Neagoe I (2020) A Comprehensive Picture of Extracellular Vesicles and Their Contents. Molecular Transfer to Cancer Cells. Cancers (Basel) 12:298

    Article  CAS  PubMed  Google Scholar 

  29. Leidal AM, Debnath J (2020) Unraveling the mechanisms that specify molecules for secretion in extracellular vesicles. Methods

    Google Scholar 

  30. Nabhan JF, Hu R, Oh RS, Cohen SN, Lu Q (2012) Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. Proc Natl Acad Sci U S A 109:4146–4151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang T, Gilkes DM, Takano N, **ang L, Luo W, Bishop CJ, Chaturvedi P, Green JJ, Semenza GL (2014) Hypoxia-inducible factors and RAB22A mediate formation of microvesicles that stimulate breast cancer invasion and metastasis. Proc Natl Acad Sci U S A 111:E3234–E3242

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Lange S, Gallagher M, Kholia S, Kosgodage US, Hristova M, Hardy J, Inal JM (2017) Peptidylarginine Deiminases-Roles in Cancer and Neurodegeneration and Possible Avenues for Therapeutic Intervention via Modulation of Exosome and Microvesicle (EMV) Release. International journal of molecular sciences 18:1196

    Article  PubMed  PubMed Central  Google Scholar 

  33. Porter AG, Jänicke RU (1999) Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6:99–104

    Article  CAS  PubMed  Google Scholar 

  34. Li B, Antonyak MA, Zhang J, Cerione RA (2012) RhoA triggers a specific signaling pathway that generates transforming microvesicles in cancer cells. Oncogene 31:4740–4749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Fatemeh M-H, Leonora B, Sara A, Pierre-Yves M, Allison EH, Alexander JT, Cesar ES, Shanice O, Christina MB, Elif S, Johan S, Winston PK (2013) Current methods for the isolation of extracellular vesicles. Biological Chemistry 394:1253–1262

    Article  Google Scholar 

  36. Simeone P, Bologna G, Lanuti P, Pierdomenico L, Guagnano TM, Pieragostino D, Del Boccio P, Vergara D, Marchisio M, Miscia S, Mariani-Costantini R (2020) Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers. International Journal of Molecular Sciences 21

    Google Scholar 

  37. Zhang Y, Liu Y, Liu H, Tang WH (2019) Exosomes: biogenesis, biologic function and clinical potential. Cell & bioscience 9:19

    Article  Google Scholar 

  38. Zhang L, Yu D (2019) Exosomes in cancer development, metastasis, and immunity Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1871:455–468

    Article  CAS  PubMed  Google Scholar 

  39. Skryabin GO, Komelkov AV, Savelyeva EE, Tchevkina EM (2020) Lipid Rafts in Exosome Biogenesis. Biochemistry (Moscow) 85:177–191

    Article  CAS  PubMed  Google Scholar 

  40. Raposo G, Stoorvogel W (2013) Extracellular vesicles: Exosomes, microvesicles, and friends. Journal of Cell Biology 200:373–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Tschuschke M, Kocherova I, Bryja A, Mozdziak P, Angelova Volponi A, Janowicz K, Sibiak R, Piotrowska-Kempisty H, Iżycki D, Bukowska D, Antosik P, Shibli JA, Dyszkiewicz-Konwińska M, Kempisty B (2020) Inclusion Biogenesis, Methods of Isolation and Clinical Application of Human Cellular Exosomes. Journal of clinical medicine 9:436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Jadli AS, Ballasy N, Edalat P, Patel VB (2020) Inside(sight) of tiny communicator: exosome biogenesis, secretion, and uptake. Molecular and Cellular Biochemistry 467:77–94

    Article  CAS  PubMed  Google Scholar 

  43. Guillaume VN, Gisela D, Graça R (2018) Shedding light on the cell biology of extracellular vesicles. Nature Reviews Molecular Cell Biology 19

    Google Scholar 

  44. Daassi D, Mahoney KM, Freeman GJ (2020) The importance of exosomal PDL1 in tumour immune evasion. Nature reviews Immunology 20:209, Bobrie A, Krumeich S, Reyal F, Recchi C, Moita LF, Seabra MC, Ostrowski M, Théry C (2012) Rab27a supports exosome-dependent and -independent mechanisms that modify the tumor microenvironment and can promote tumor progression. Cancer Res 72:4920–4930

    Google Scholar 

  45. Chen B-Y, Sung CW-H, Chen C, Cheng C-M, Lin DP-C, Huang C-T, Hsu M-Y (2019) Advances in exosomes technology. Clinica Chimica Acta 493:14–19

    Article  CAS  Google Scholar 

  46. Doyle LM, Wang MZ (2019) Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells 8:727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hou R, Li Y, Sui Z, Yuan H, Yang K, Liang Z, Zhang L, Zhang Y (2019) Advances in exosome isolation methods and their applications in proteomic analysis of biological samples. Anal Bioanal Chem 411:5351–5361

    Article  CAS  PubMed  Google Scholar 

  48. Yang D, Zhang W, Zhang H, Zhang F, Chen L, Ma L, Larcher LM, Chen S, Liu N, Zhao Q, Tran PHL, Chen C, Veedu RN, Wang T (2020) Progress, opportunity, and perspective on exosome isolation - efforts for efficient exosome-based theranostics. Theranostics 10:3684–3707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Sun L, Meckes DG, Jr (2018) Methodological Approaches to Study Extracellular Vesicle miRNAs in Epstein−Barr Virus-Associated Cancers. International journal of molecular sciences 19:2810

    Article  PubMed  PubMed Central  Google Scholar 

  50. Sadik N, Cruz L, Gurtner A, Rodosthenous RS, Dusoswa SA, Ziegler O, Van Solinge TS, Wei Z, Salvador-Garicano AM, Gyorgy B, Broekman M, Balaj L (2018) Extracellular RNAs: A New Awareness of Old Perspectives.

    Google Scholar 

  51. Ludwig N, Whiteside TL, Reichert TE (2019) Challenges in Exosome Isolation and Analysis in Health and Disease. Int J Mol Sci 20

    Google Scholar 

  52. Brennan K, Martin K, FitzGerald SP, O’Sullivan J, Wu Y, Blanco A, Richardson C, Mc Gee MM (2020) A comparison of methods for the isolation and separation of extracellular vesicles from protein and lipid particles in human serum. Scientific Reports 10:1039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, Dingli F, Loew D, Tkach M, Th\‘ery C (2016) Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. National Academy of Sciences,

    Google Scholar 

  54. Van Deun J, Jo A, Li H, Lin H-Y, Weissleder R, Im H, Lee H (2020) Integrated Dual-Mode Chromatography to Enrich Extracellular Vesicles from Plasma. Advanced Biosystems n/a:1900310

    Google Scholar 

  55. Konoshenko MY, Lekchnov EA, Vlassov AV, Laktionov PP (2018) Isolation of Extracellular Vesicles: General Methodologies and Latest Trends. BioMed research international 2018:8545347

    Article  PubMed  PubMed Central  Google Scholar 

  56. Benedikter BJ, Bouwman FG, Vajen T, Heinzmann ACA, Grauls G, Mariman EC, Wouters EFM, Savelkoul PH, Lopez-Iglesias C, Koenen RR, Rohde GGU, Stassen FRM (2017) Ultrafiltration combined with size exclusion chromatography efficiently isolates extracellular vesicles from cell culture media for compositional and functional studies. Scientific Reports 7:15297

    Article  PubMed  PubMed Central  Google Scholar 

  57. Gurunathan S, Kang MH, Jeyaraj M, Qasim M, Kim JH (2019) Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes. Cells 8

    Google Scholar 

  58. Stranska R, Gysbrechts L, Wouters J, Vermeersch P, Bloch K, Dierickx D, Andrei G, Snoeck R (2018) Comparison of membrane affinity-based method with size-exclusion chromatography for isolation of exosome-like vesicles from human plasma. J Transl Med 16:1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Xu R, Fitts A, Li X, Fernandes J, Pochampally R, Mao J, Liu YM (2016) Quantification of Small Extracellular Vesicles by Size Exclusion Chromatography with Fluorescence Detection. Anal Chem 88:10390–10394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Zhang H, Lyden D (2019) Asymmetric-flow field-flow fractionation technology for exomere and small extracellular vesicle separation and characterization. Nature Protocols 14:1027–1053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Logozzi M, De Milito A, Lugini L, Borghi M, Calabrò L, Spada M, Perdicchio M, Marino ML, Federici C, Iessi E, Brambilla D, Venturi G, Lozupone F, Santinami M, Huber V, Maio M, Rivoltini L, Fais S (2009) High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients. PLoS One 4:e5219

    Article  PubMed  PubMed Central  Google Scholar 

  62. Gheinani AH, Vögeli M, Baumgartner U, Vassella E, Draeger A, Burkhard FC, Monastyrskaya K (2018) Improved isolation strategies to increase the yield and purity of human urinary exosomes for biomarker discovery. Scientific Reports 8:3945

    Article  PubMed  PubMed Central  Google Scholar 

  63. Tang YT, Huang YY, Zheng L, Qin SH, Xu XP, An TX, Xu Y, Wu YS, Hu XM, ** BH, Wang Q (2017) Comparison of isolation methods of exosomes and exosomal RNA from cell culture medium and serum. Int J Mol Med 40:834–844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Li G, Tang W, Yang F (2020) Cancer Liquid Biopsy Using Integrated Microfluidic Exosome Analysis Platforms. Biotechnol J 15:e1900225

    Article  PubMed  Google Scholar 

  65. Rho J, Chung J, Im H, Liong M, Shao H, Castro CM, Weissleder R, Lee H (2013) Magnetic nanosensor for detection and profiling of erythrocyte-derived microvesicles. ACS Nano 7:11227–11233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Wunsch BH, Smith JT, Gifford SM, Wang C, Brink M, Bruce RL, Austin RH, Stolovitzky G, Astier Y (2016) Nanoscale lateral displacement arrays for the separation of exosomes and colloids down to 20 nm. Nat Nanotechnol 11:936–940

    Article  CAS  PubMed  Google Scholar 

  67. Lee K, Shao H, Weissleder R, Lee H (2015) Acoustic purification of extracellular microvesicles. ACS Nano 9:2321–2327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kanwar SS, Dunlay CJ, Simeone DM, Nagrath S (2014) Microfluidic device (ExoChip) for on-chip isolation, quantification and characterization of circulating exosomes. Lab Chip 14:1891–1900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Zhao Z, Yang Y, Zeng Y, He M (2016) A microfluidic ExoSearch chip for multiplexed exosome detection towards blood-based ovarian cancer diagnosis. Lab Chip 16:489–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sokolova V, Ludwig AK, Hornung S, Rotan O, Horn PA, Epple M, Giebel B (2011) Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy. Colloids Surf B Biointerfaces 87:146–150

    Article  CAS  PubMed  Google Scholar 

  71. Szatanek R, Baj-Krzyworzeka M, Zimoch J, Lekka M, Siedlar M, Baran J (2017) The Methods of Choice for Extracellular Vesicles (EVs) Characterization. Int J Mol Sci 18

    Google Scholar 

  72. Filipe V, Hawe A, Jiskoot W (2010) Critical Evaluation of Nanoparticle Tracking Analysis (NTA) by NanoSight for the Measurement of Nanoparticles and Protein Aggregates. Pharmaceutical Research 27:796–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Cizmar P, Yuana Y (2017) Detection and Characterization of Extracellular Vesicles by Transmission and Cryo-Transmission Electron Microscopy. In: (eds) 1660.

    Google Scholar 

  74. Shao H, Im H, Castro CM, Breakefield X, Weissleder R, Lee H (2018) New Technologies for Analysis of Extracellular Vesicles. Chem Rev 118:1917–1950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Mateos JM, Barmettler G, Doehner J, Kaech A, Ziegler U (2018) Direct imaging of uncoated biological samples enables correlation of super-resolution and electron microscopy data. Scientific Reports 8

    Google Scholar 

  76. Sharma S, LeClaire M, Gimzewski JK (2018) Ascent of atomic force microscopy as a nanoanalytical tool for exosomes and other extracellular vesicles. Nanotechnology 29:132001

    Article  CAS  PubMed  Google Scholar 

  77. Olcum S, Cermak N, Wasserman SC, Christine KS, Atsumi H, Payer KR, Shen W, Lee J, Belcher AM, Bhatia SN, Manalis SR (2014) Weighing nanoparticles in solution at the attogram scale. Proc Natl Acad Sci U S A 111:1310–1315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Maas SLN, Broekman MLD, de Vrij J (2017) Tunable Resistive Pulse Sensing for the Characterization of Extracellular Vesicles Exosomes and Microvesicles: Methods and Protocols. In: Hill AF (ed) Springer New York, New York, NY

    Google Scholar 

  79. Bandu R, Oh JW, Kim KP (2019) Mass spectrometry-based proteome profiling of extracellular vesicles and their roles in cancer biology. Exp Mol Med 51:1–10, Cañas B, López-Ferrer D, Ramos-Fernández A, Camafeita E, Calvo E (2006) Mass spectrometry technologies for proteomics. Briefings in Functional Genomics 4:295–320,Schey KL, Luther JM, Rose KL (2015) Proteomics characterization of exosome cargo. Methods 87:75–82

    Google Scholar 

  80. Jachimowicz LA, Ye P, Lu Y, Guenther G, Nancy LI (2019) Detection of small particles by flow cytometry: Analysis of small particle beads and extracellular vesicles. The Journal of Immunology 202:130.17

    Google Scholar 

  81. Mastoridis S, Bertolino GM, Whitehouse G, Dazzi F, Sanchez-Fueyo A, Martinez-Llordella M (2018) Multiparametric Analysis of Circulating Exosomes and Other Small Extracellular Vesicles by Advanced Imaging Flow Cytometry. Frontiers in Immunology 9:1583, Görgens A, Bremer M, Ferrer-Tur R, Murke F, Tertel T, Horn PA, Thalmann S, Welsh JA, Probst C, Guerin C, Boulanger CM, Jones JC, Hanenberg H, Erdbrügger U, Lannigan J, Ricklefs FL, El-Andaloussi S, Giebel B (2019) Optimisation of imaging flow cytometry for the analysis of single extracellular vesicles by using fluorescence-tagged vesicles as biological reference material. Journal of Extracellular Vesicles 8:1587567

    Google Scholar 

  82. Im H, Shao H, Park YI, Peterson VM, Castro CM, Weissleder R, Lee H (2014) Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nature biotechnology 32:490–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Jeong S, Park J, Pathania D, Castro CM, Weissleder R, Lee H (2016) Integrated Magneto-Electrochemical Sensor for Exosome Analysis. ACS Nano 10:1802–1809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Wei F, Yang J, Wong DTW (2013) Detection of exosomal biomarker by electric field-induced release and measurement (EFIRM). Biosens Bioelectron 44:115–121

    Article  CAS  PubMed  Google Scholar 

  85. 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. Nature Cell Biology 9:654–659

    Article  CAS  PubMed  Google Scholar 

  86. Silva M, Melo SA (2015) Non-coding RNAs in Exosomes: New Players in Cancer Biology. Current genomics 16:295–303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Balaj L, Lessard R, Dai L, Cho YJ, Pomeroy SL, Breakefield XO, Skog J (2011) Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat Commun 2:180, Thakur BK, Zhang H, Becker A, Matei I, Huang Y, Costa-Silva B, Zheng Y, Hoshino A, Brazier H, **ang J, Williams C, Rodriguez-Barrueco R, Silva JM, Zhang W, Hearn S, Elemento O, Paknejad N, Manova-Todorova K, Welte K, Bromberg J, Peinado H, Lyden D (2014) Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res 24:766–769

    Google Scholar 

  88. Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT, Jr, Carter BS, Krichevsky AM, Breakefield XO (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nature cell biology 10:1470–1476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Zheng H, Zhan Y, Liu S, Lu J, Luo J, Feng J, Fan S (2018) The roles of tumor-derived exosomes in non-small cell lung cancer and their clinical implications. Journal of experimental & clinical cancer research:CR 37:226

    Article  Google Scholar 

  90. Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, LeBleu VS, Mittendorf EA, Weitz J, Rahbari N, Reissfelder C, Pilarsky C, Fraga MF, Piwnica-Worms D, Kalluri R (2015) Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 523:177–182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Takahashi K, Yan IK, Kim C, Kim J, Patel T (2014) Analysis of extracellular RNA by digital PCR. Frontiers in oncology 4:129

    Article  PubMed  PubMed Central  Google Scholar 

  92. Taylor SC, Laperriere G, Germain H (2017) Droplet Digital PCR versus qPCR for gene expression analysis with low abundant targets: from variable nonsense to publication quality data. Sci Rep 7:2409

    Article  PubMed  PubMed Central  Google Scholar 

  93. Chen WW, Balaj L, Liau LM, Samuels ML, Kotsopoulos SK, Maguire CA, LoGuidice L, Soto H, Garrett M, Zhu LD, Sivaraman S, Chen C, Wong ET, Carter BS, Hochberg FH, Breakefield XO, Skog J (2013) BEAMing and Droplet Digital PCR Analysis of Mutant IDH1 mRNA in Glioma Patient Serum and Cerebrospinal Fluid Extracellular Vesicles. Molecular Therapy - Nucleic Acids 2

    Google Scholar 

  94. Wang C, Ding Q, Plant P, Basheer M, Yang C, Tawedrous E, Krizova A, Boulos C, Farag M, Cheng Y, Yousef GM (2019) Droplet digital PCR improves urinary exosomal miRNA detection compared to real-time PCR. Clin Biochem 67:54–59

    Article  CAS  PubMed  Google Scholar 

  95. Notarangelo M, Zucal C, Modelska A, Pesce I, Scarduelli G, Potrich C, Lunelli L, Pederzolli C, Pavan P, la Marca G, Pasini L, Ulivi P, Beltran H, Demichelis F, Provenzani A, Quattrone A, D’Agostino VG (2019) Ultrasensitive detection of cancer biomarkers by nickel-based isolation of polydisperse extracellular vesicles from blood. EBioMedicine 43:114–126

    Article  PubMed  PubMed Central  Google Scholar 

  96. Cheng Y-S, Zheng Y, VanderGheynst JS (2011) Rapid Quantitative Analysis of Lipids Using a Colorimetric Method in a Microplate Format. Lipids 46:95–103

    Article  CAS  PubMed  Google Scholar 

  97. Skotland T, Sagini K, Sandvig K, Llorente A (2020) An emerging focus on lipids in extracellular vesicles. Lipids in disease pathology, diagnosis & therapy 159:308–321

    CAS  Google Scholar 

  98. Zebrowska A, Skowronek A, Wojakowska A, Widlak P, Pietrowska M (2019) Metabolome of Exosomes: Focus on Vesicles Released by Cancer Cells and Present in Human Body Fluids. International journal of molecular sciences 20:3461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Zebrowska A, Skowronek A, Wojakowska A, Widlak P, Pietrowska M (2019) Metabolome of Exosomes: Focus on Vesicles Released by Cancer Cells and Present in Human Body Fluids. International journal of molecular sciences 20:3461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Hessvik NP, Llorente A (2018) Current knowledge on exosome biogenesis and release. Cell Mol Life Sci 75:193–208, Andreu Z, Yáñez-Mó M (2014) Tetraspanins in extracellular vesicle formation and function. Frontiers in immunology 5:442

    Google Scholar 

  101. Yu D-d, Wu Y, Shen H-y, Lv M-m, Chen W-x, Zhang X-h, Zhong S-l, Tang J-h, Zhao J-h (2015) Exosomes in development, metastasis and drug resistance of breast cancer. Cancer Sci 106:959–964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Taylor DD, Gercel-Taylor C (2008) MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 110:13–21

    Article  CAS  PubMed  Google Scholar 

  103. Osti D, Del Bene M, Rappa G, Santos M, Matafora V, Richichi C, Faletti S, Beznoussenko GV, Mironov A, Bachi A, Fornasari L, Bongetta D, Gaetani P, DiMeco F, Lorico A, Pelicci G (2019) Clinical Significance of Extracellular Vesicles in Plasma from Glioblastoma Patients. Clin Cancer Res 25:266–276

    Article  CAS  PubMed  Google Scholar 

  104. Moon PG, Lee JE, Cho YE, Lee SJ, Jung JH, Chae YS, Bae HI, Kim YB, Kim IS, Park HY, Baek MC (2016) Identification of Developmental Endothelial Locus-1 on Circulating Extracellular Vesicles as a Novel Biomarker for Early Breast Cancer Detection. Clin Cancer Res 22:1757–1766

    Article  CAS  PubMed  Google Scholar 

  105. Roca E, Lacroix R, Judicone C, Laroumagne S, Robert S, Cointe S, Muller A, Kaspi E, Roll P, Brisson AR, Tantucci C, Astoul P, Dignat-George F (2016) Detection of EpCAM-positive microparticles in pleural fluid: A new approach to mini-invasively identify patients with malignant pleural effusions. Oncotarget 7:3357–3366

    Article  PubMed  Google Scholar 

  106. Hanif F, Muzaffar K, Perveen K, Malhi SM, Simjee SU (2017) Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation and Treatment. Asian Pac J Cancer Prev 18:3–9

    PubMed  PubMed Central  Google Scholar 

  107. An Z, Aksoy O, Zheng T, Fan Q-W, Weiss WA (2018) Epidermal growth factor receptor and EGFRvIII in glioblastoma: signaling pathways and targeted therapies. Oncogene 37:1561–1575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Tominaga N, Kosaka N, Ono M, Katsuda T, Yoshioka Y, Tamura K, Lötvall J, Nakagama H, Ochiya T (2015) Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood–brain barrier. Nature Communications 6:6716

    Article  CAS  PubMed  Google Scholar 

  109. Burges A, Schmalfeldt B (2011) Ovarian cancer: diagnosis and treatment. Dtsch Arztebl Int 108:635–641

    PubMed  PubMed Central  Google Scholar 

  110. Doubeni CA, Doubeni AR, Myers AE (2016) Diagnosis and Management of Ovarian Cancer. Am Fam Physician 93:937–944

    PubMed  Google Scholar 

  111. Pignata S, Cannella L, Leopardo D, Bruni GS, Facchini G, Pisano C (2011) Follow-up with CA125 after primary therapy of advanced ovarian cancer: in favor of continuing to prescribe CA125 during follow-up. Annals of Oncology,8th International Symposium on Advanced Ovarian Cancer: Optimal Therapy 4 March 2011, Valencia, Spain 22:viii40–viii44

    Google Scholar 

  112. Testa U, Petrucci E, Pasquini L, Castelli G, Pelosi E (2018) Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells. Medicines (Basel) 5:16

    Article  PubMed  Google Scholar 

  113. Tran PH-L, **ang D, Nguyen TN-G, Tran TT-D, Chen Q, Yin W, Zhang Y, Kong L, Duan A, Chen K, Sun M, Li Y, Hou Y, Zhu Y, Ma Y, Jiang G, Duan W (2020) Aptamer-guided extracellular vesicle theranostics in oncology. Theranostics 10:3849–3866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Rawla P, Sunkara T, Gaduputi V (2019) Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World journal of oncology 10:10–27

    Article  PubMed  PubMed Central  Google Scholar 

  115. Ilic M, Ilic I (2016) Epidemiology of pancreatic cancer. World journal of gastroenterology 22:9694–9705

    Article  PubMed  PubMed Central  Google Scholar 

  116. Ballehaninna UK, Chamberlain RS (2012) The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal. J Gastrointest Oncol 3:105–119

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Machida T, Tomofuji T, Maruyama T, Yoneda T, Ekuni D, Azuma T, Miyai H, Mizuno H, Kato H, Tsutsumi K, Uchida D, Takaki A, Okada H, Morita M (2016) miR-1246 and miR-4644 in salivary exosome as potential biomarkers for pancreatobiliary tract cancer. Oncol Rep 36:2375–2381

    Article  CAS  PubMed  Google Scholar 

  118. Yang KS, Im H, Hong S, Pergolini I, Del Castillo AF, Wang R, Clardy S, Huang C-H, Pille C, Ferrone S, Yang R, Castro CM, Lee H, Del Castillo CF, Weissleder R (2017) Multiparametric plasma EV profiling facilitates diagnosis of pancreatic malignancy. Science translational medicine 9:eaal3226

    Article  PubMed  PubMed Central  Google Scholar 

  119. Brenner H, Kloor M, Pox CP (2014) Colorectal cancer. Lancet 383:1490–1502

    Article  PubMed  Google Scholar 

  120. Ruiz-López L, Blancas I, Garrido JM, Mut-Salud N, Moya-Jódar M, Osuna A, Rodríguez-Serrano F (2018) The role of exosomes on colorectal cancer: A review. Journal of Gastroenterology and Hepatology 33:792–799

    Article  PubMed  Google Scholar 

  121. Li J, Li B, Ren C, Chen Y, Guo X, Zhou L, Peng Z, Tang Y, Chen Y, Liu W, Zhu B, Wang L, Liu X, Shi X, Peng Z (2017) The clinical significance of circulating GPC1 positive exosomes and its regulative miRNAs in colon cancer patients. Oncotarget 8:101189–101202

    Article  PubMed  PubMed Central  Google Scholar 

  122. Hao Y, Li Y, Ye M, Guo Y, Li Q, Peng X, Wang Q, Zhang S, Zhao H, Zhang H, Li G, Zhu J, **ao W (2017) KRAS and BRAF mutations in serum exosomes from patients with colorectal cancer in a Chinese population. Oncology Letters 13

    Google Scholar 

  123. Ogata-Kawata H, Izumiya M, Kurioka D, Honma Y, Yamada Y, Furuta K, Gunji T, Ohta H, Okamoto H, Sonoda H, Watanabe M, Nakagama H, Yokota J, Kohno T, Tsuchiya N (2014) Circulating exosomal microRNAs as biomarkers of colon cancer. PLoS One 9:e92921

    Article  PubMed  PubMed Central  Google Scholar 

  124. Bade BC, Dela Cruz CS (2020) Lung Cancer 2020. Clinics in Chest Medicine 41:1–24

    Article  PubMed  Google Scholar 

  125. Zappa C, Mousa SA (2016) Non-small cell lung cancer: current treatment and future advances. Translational lung cancer research 5:288–300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ, Wu Y-L, Paz-Ares L (2017) Lung cancer: current therapies and new targeted treatments. The Lancet 389:299–311

    Article  CAS  Google Scholar 

  127. Rolfo C (2016) Exosomal Proteins in Lung Cancer: The Last Frontier in Liquid Biopsies. J Thorac Oncol 11:1609–1611

    Article  PubMed  Google Scholar 

  128. Brinkmann K, Enderle D, Koestler T, Bentink S, Emenegger J, Spiel A, Mueller R, O\textquoterightNeill V, Skog J, Noerholm M (2015) Abstract 545: Plasma-based diagnostics for detection of EML4-ALK fusion transcripts in NSCLC patients. American Association for Cancer Research,

    Google Scholar 

  129. Reclusa P, Taverna S, Pucci M, Durendez E, Calabuig S, Manca P, Serrano MJ, Sober L, Pauwels P, Russo A, Rolfo C (2017) Exosomes as diagnostic and predictive biomarkers in lung cancer. Journal of thoracic disease 9:S1373–S1382

    Article  PubMed  PubMed Central  Google Scholar 

  130. Li Y, Zhang Y, Qiu F, Qiu Z (2011) Proteomic identification of exosomal LRG1: a potential urinary biomarker for detecting NSCLC. Electrophoresis 32:1976–1983

    Article  CAS  PubMed  Google Scholar 

  131. Saini S (2016) PSA and beyond: alternative prostate cancer biomarkers. Cellular oncology (Dordrecht) 39:97–106

    Article  CAS  PubMed  Google Scholar 

  132. McKiernan J, Donovan MJ, O’Neill V, Bentink S, Noerholm M, Belzer S, Skog J, Kattan MW, Partin A, Andriole G, Brown G, Wei JT, Thompson IM, Jr, Carroll P (2016) A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer at Initial Biopsy. JAMA Oncology 2:882–889

    Article  PubMed  Google Scholar 

  133. Minciacchi VR, Zijlstra A, Rubin MA, Di Vizio D (2017) Extracellular vesicles for liquid biopsy in prostate cancer: where are we and where are we headed. Prostate Cancer Prostatic Dis 20:251–258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Sánchez CA, Andahur EI, Valenzuela R, Castellón EA, Fullá JA, Ramos CG, Triviño JC (2016) Exosomes from bulk and stem cells from human prostate cancer have a differential microRNA content that contributes cooperatively over local and pre-metastatic niche. Oncotarget 7:3993–4008

    Article  PubMed  Google Scholar 

  135. Waks AG, Winer EP (2019) Breast Cancer Treatment. JAMA 321:316,Harbeck N, Gnant M (2017) Breast cancer. The Lancet 389:1134–1150

    Google Scholar 

  136. Rupp A-K, Rupp C, Keller S, Brase JC, Ehehalt R, Fogel M, Moldenhauer G, Marmé F, Sültmann H, Altevogt P (2011) Loss of EpCAM expression in breast cancer derived serum exosomes: Role of proteolytic cleavage. Gynecologic Oncology 122:437–446, Green TM, Alpaugh ML, Barsky SH, Rappa G, Lorico A (2015) Breast Cancer-Derived Extracellular Vesicles: Characterization and Contribution to the Metastatic Phenotype. BioMed Research International 2015:634865,Ciravolo V, Huber V, Ghedini GC, Venturelli E, Bianchi F, Campiglio M, Morelli D, Villa A, Mina PD, Menard S, Filipazzi P, Rivoltini L, Tagliabue E, Pupa SM (2012) Potential role of HER2-overexpressing exosomes in countering trastuzumab-based therapy. Journal of Cellular Physiology 227:658–667

    Google Scholar 

  137. Menck K, Scharf C, Bleckmann A, Dyck L, Rost U, Wenzel D, Dhople VM, Siam L, Pukrop T, Binder C, Klemm F (2015) Tumor-derived microvesicles mediate human breast cancer invasion through differentially glycosylated EMMPRIN. J Mol Cell Biol 7:143–153

    Article  CAS  PubMed  Google Scholar 

  138. Galindo-Hernandez O, Villegas-Comonfort S, Candanedo F, González-Vázquez MC, Chavez-Ocaña S, Jimenez-Villanueva X, Sierra-Martinez M, Salazar EP (2013) Elevated concentration of microvesicles isolated from peripheral blood in breast cancer patients. Arch Med Res 44:208–214

    Article  CAS  PubMed  Google Scholar 

  139. Yang SJ, Wang DD, Li J, Xu HZ, Shen HY, Chen X, Zhou SY, Zhong SL, Zhao JH, Tang JH (2017) Predictive role of GSTP1-containing exosomes in chemotherapy-resistant breast cancer. Gene 623:5–14

    Article  CAS  PubMed  Google Scholar 

  140. König L, Kasimir-Bauer S, Bittner A-K, Hoffmann O, Wagner B, Santos Manvailer LF, Kimmig R, Horn PA, Rebmann V (2017) Elevated levels of extracellular vesicles are associated with therapy failure and disease progression in breast cancer patients undergoing neoadjuvant chemotherapy. Oncoimmunology 7:e1376153

    Article  PubMed  PubMed Central  Google Scholar 

  141. Abbas O, Miller DD, Bhawan J (2014) Cutaneous malignant melanoma: update on diagnostic and prognostic biomarkers. Am J Dermatopathol 36:363–379

    Article  PubMed  Google Scholar 

  142. Peinado H, Alečković M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, García-Santos G, Ghajar C, Nitadori-Hoshino A, Hoffman C, Badal K, Garcia BA, Callahan MK, Yuan J, Martins VR, Skog J, Kaplan RN, Brady MS, Wolchok JD, Chapman PB, Kang Y, Bromberg J, Lyden D (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nature medicine 18:883–891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Alegre E, Zubiri L, Perez-Gracia JL, González-Cao M, Soria L, Martín-Algarra S, González A (2016) Circulating melanoma exosomes as diagnostic and prognosis biomarkers. Clin Chim Acta 454:28–32

    Article  CAS  PubMed  Google Scholar 

  144. Zhang Q, Higginbotham JN, Jeppesen DK, Yang YP, Li W, McKinley ET, Graves-Deal R, ** J, Britain CM, Dorsett KA, Hartman CL, Ford DA, Allen RM, Vickers KC, Liu Q, Franklin JL, Bellis SL, Coffey RJ (2019) Transfer of Functional Cargo in Exomeres. Cell Rep 27:940–954.e6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Ma L, Li Y, Peng J, Wu D, Zhao X, Cui Y, Chen L, Yan X, Du Y, Yu L (2015) Discovery of the migrasome, an organelle mediating release of cytoplasmic contents during cell migration. Cell Res 25:24–38

    Article  CAS  PubMed  Google Scholar 

  146. Ciardiello C, Leone A, Lanuti P, Roca MS, Moccia T, Minciacchi VR, Minopoli M, Gigantino V, De Cecio R, Rippa M, Petti L, Capone F, Vitagliano C, Milone MR, Pucci B, Lombardi R, Iannelli F, Di Gennaro E, Bruzzese F, Marchisio M, Carriero MV, Di Vizio D, Budillon A (2019) Large oncosomes overexpressing integrin alpha-V promote prostate cancer adhesion and invasion via AKT activation. J Exp Clin Cancer Res 38:317

    Article  PubMed  PubMed Central  Google Scholar 

  147. Nieri D, Neri T, Petrini S, Vagaggini B, Paggiaro P, Celi A (2016) Cell-derived microparticles and the lung. Eur Respir Rev 25:266–277

    Article  PubMed  PubMed Central  Google Scholar 

  148. Cocucci E, Meldolesi J (2015) Ectosomes and exosomes: shedding the confusion between extracellular vesicles. Trends in Cell Biology 25:364–372

    Article  CAS  PubMed  Google Scholar 

  149. van Herwijnen MJ, Zonneveld MI, Goerdayal S, Nolte-’t Hoen EN, Garssen J, Stahl B, Maarten Altelaar AF, Redegeld FA, Wauben MH (2016) Comprehensive Proteomic Analysis of Human Milk-derived Extracellular Vesicles Unveils a Novel Functional Proteome Distinct from Other Milk Components. Mol Cell Proteomics 15:3412–3423

    Article  PubMed  PubMed Central  Google Scholar 

  150. Wu J, Hu S, Zhang L, **n J, Sun C, Wang L, Ding K, Wang B (2020) Tumor circulome in the liquid biopsies for cancer diagnosis and prognosis. Theranostics 10:4544–4556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Zhao Z, Fan J, Hsu Y-MS, Lyon CJ, Ning B, Hu TY (2019) Extracellular vesicles as cancer liquid biopsies: from discovery, validation, to clinical application. Lab on a Chip 19:1114–1140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. De Rubis G, Rajeev Krishnan S, Bebawy M (2019) Liquid Biopsies in Cancer Diagnosis, Monitoring, and Prognosis. Trends in Pharmacological Sciences 40:172–186

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Michelle A. Garlin Politis, Hyungsoon Im, Cesar M. Castro & Hakho Lee

  2. Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Michelle A. Garlin Politis, Hyungsoon Im & Hakho Lee

  3. Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Bob S. Carter & Leonora Balaj

  4. Exosome Diagnostics, Inc, Waltham, MA, USA

    Johan Skog

  5. Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Cesar M. Castro

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  1. Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA

    Richard J. Cote

  2. ACTC Lab, Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Athens, Greece

    Evi Lianidou

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Garlin Politis, M.A. et al. (2023). Translational Opportunities of Extracellular Vesicles in Biomedicine. In: Cote, R.J., Lianidou, E. (eds) Circulating Tumor Cells. Current Cancer Research. Springer, Cham. https://doi.org/10.1007/978-3-031-22903-9_4

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