Skip to content
naulon
Get started

No retraction, correction or concern found when last checked on Oct 21, 2026.

Tumor-derived extracellular vesicles: reliable tools for Cancer diagnosis and clinical applications

Reza Rahbarghazi, Nasrollah Jabbari, Neda Abbaspour Sani and 8 more

Cell Communication and Signaling · 2019 · Review · CC BY

doi:10.1186/s12964-019-0390-y

Abstract

Background. Studies have recently revealed that almost every type of cells including tumor cells abundantly release small vesicles known as extracellular vesicles (EVs) into the extracellular milieu. EVs carry a repertoire of biological molecules including nucleic acids, proteins, lipids, and carbohydrates and transport their cargo between cells in the vicinity as well as distantly located cells and hence act as messengers of intercellular communication. In this review, we aimed to discuss the tumor-derived exosome biology and the pivotal roles of exosomes in cancer diagnosis and treatment.

Methods. In the present review study, the authors studied several articles over the past two decades published on the kinetics of EVs in tumor environment as well as on the application of these vesicles in cancer diagnosis and therapy.

Results. A growing body of evidence indicates that nucleic acids such as microRNAs (miRNAs) transferring by EVs participate to create a conducive tumor environment. As EV-associated miRNAs are tissue-specific and present in most biological fluids, they hold great potential for clinical application in cancer early diagnosis, prognosis, and treatment response. Furthermore, exosomes can serve as drug delivery vehicles transferring miRNAs as well as therapeutic agents to target cells. These nano-vesicles exhibit ideal properties in comparison with the synthetic carriers that attracted scientist’s attention in the field of nanotechnology medicine. Scientists have employed different strategies to build exosomes-based drug delivery system. In general, two methods (direct engineering and indirect engineering) are being utilized to produce artificial exosomes. Para-clinical data have confirmed the beneficial effects of engineering exosomes in cancer therapy.

Conclusion. Exosomal miRNAs hold great promise for clinical application in early diagnosis and treatment of cancers. In addition, in spite of enthusiastic results obtained by engineered exosomes, however, there is an increasing concern over the use of optimal methods for engineering exosomes and the safety of engineered exosomes in clinical trials is still unclear.

References 147

  1. 1.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA: Cancer J Clin. 2017;67:7-30.

    Not in our library10.3322/caac.21387

  2. 2.

    Kamińska K, Szczylik C, Bielecka ZF, Bartnik E, Porta C, Lian F, Czarnecka AM. The role of the cell–cell interactions in cancer progression. JCMM. 2015;19:283-296.

    Not in our library10.1111/jcmm.12408

  3. 3.

    Schiffman JD, Fisher PG, Gibbs P. Early detection of cancer: past, present, and future. Am Soc Clin Oncol Educ Book. 2015;35:57-65.

    Not in our library10.14694/edbook_am.2015.35.57

  4. 4.

    Shyamala K, Girish H, Murgod S. Risk of tumor cell seeding through biopsy and aspiration cytology. J Int Soc Prev Community Dent. 2014;4:5.

    Not in our library10.4103/2231-0762.129446

  5. 5.

    Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol. 2013;10:472.

    Not in our library10.1038/nrclinonc.2013.110

  6. 6.

    Skog J, Würdinger T, Van Rijn S, Meijer DH, Gainche L, Curry WT, Carter BS, Krichevsky AM, Breakefield XO. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10:1470.

    Not in our library10.1038/ncb1800

  7. 7.

    Fatima F, Nawaz M. Vesiculated long non-coding RNAs: offshore packages deciphering trans-regulation between cells, cancer progression and resistance to therapies. Noncoding RNA. 2017;3:10.

    Not in our library10.3390/ncrna3010010

  8. 8.

    Cazzoli R, Buttitta F, Di Nicola M, Malatesta S, Marchetti A, Rom WN, Pass HI. microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J Thorac Oncol. 2013;8:1156-1162.

    Not in our library10.1097/jto.0b013e318299ac32

  9. 9.

    Nawaz M, Camussi G, Valadi H, Nazarenko I, Ekström K, Wang X, Principe S, Shah N, Ashraf NM, Fatima F. The emerging role of extracellular vesicles as biomarkers for urogenital cancers. Nat Rev Urol. 2014;11:688.

    Not in our library10.1038/nrurol.2014.301

  10. 10.

    Nawaz M, Fatima F, Nazarenko I, Ekström K, Murtaza I, Anees M, Sultan A, Neder L, Camussi G, Valadi H. Extracellular vesicles in ovarian cancer: applications to tumor biology, immunotherapy and biomarker discovery. Expert Rev Proteomics. 2016;13:395-409.

    Not in our library10.1586/14789450.2016.1165613

  11. 11.

    Mateescu B, Kowal EJ, Van Balkom BW, Bartel S, Bhattacharyya SN, Buzás EI, Buck AH, De Candia P, Chow FW, Das S. Obstacles and opportunities in the functional analysis of extracellular vesicle RNA–an ISEV position paper. J Extracell Vesicles. 2017;6:1286095.

    Not in our library10.1080/20013078.2017.1286095

  12. 12.

    Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200:373-383.

    Not in our library10.1083/jcb.201211138

  13. 13.

    Colombo M, Moita C, van Niel G, Kowal J, Vigneron J, Benaroch P, Manel N, Moita LF, Théry C, Raposo G. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci. 2013. 10.1242/jcs.12886.

    Not in our library10.1242/jcs.128868

  14. 14.

    Taylor DD, Zacharias W, Gercel-Taylor C. Exosome isolation for proteomic analyses and RNA profiling. Serum/Plasma Proteomics. New York: Humana Press. Methods Mol Biol. 2011;728:235–46.

    Not in our library10.1007/978-1-61779-068-3_15

  15. 15.
    Dendritic Cell-Derived Exosomes may be a Tool for Cancer Immunotherapy by Converting Tumor Cells into Immunogenic Targets · 2015
    No notice
  16. 16.

    Malhotra H, Sheokand N, Kumar S, Chauhan AS, Kumar M, Jakhar P, Boradia VM, Raje CI, Raje M. Exosomes: tunable nano vehicles for macromolecular delivery of transferrin and lactoferrin to specific intracellular compartment. J Biomed Nanotechnol. 2016;12:1101-1114.

    Not in our library10.1166/jbn.2016.2229

  17. 17.

    Mathiyalagan P, Sahoo S. Exosomes-based gene therapy for microRNA delivery. New York: Humana Press. Methods Mol Biol. 2017;1521:139–52.

    Not in our library10.1007/978-1-4939-6588-5_9

  18. 18.

    Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, de Gruijl TD, Würdinger T, Middeldorp JM. Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci U S A. 2010;107:6328-6333.

    Not in our library10.1073/pnas.0914843107

  19. 19.

    Tian Y, Li S, Song J, Ji T, Zhu M, Anderson GJ, Wei J, Nie G. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials. 2014;35:2383-2390.

    Not in our library10.1016/j.biomaterials.2013.11.083

  20. 20.

    Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. 2010;12:19.

    Not in our library10.1038/ncb2000

  21. 21.

    György B, Szabó TG, Pásztói M, Pál Z, Misják P, Aradi B, László V, Pállinger E, Pap E, Kittel A. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci. 2011;68:2667-2688.

    Not in our library10.1007/s00018-011-0689-3

  22. 22.

    Kowal J, Tkach M, Thery C. Biogenesis and secretion of exosomes. Curr Opin Cell Biol. 2014;29:116-125.

    Not in our library10.1016/j.ceb.2014.05.004

  23. 23.

    Théry Clotilde, Amigorena Sebastian, Raposo Graça, Clayton Aled. Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids. Current Protocols in Cell Biology. 2006;30(1):3.22.1-3.22.29.

    Not in our library10.1002/0471143030.cb0322s30

  24. 24.
    Cells release subpopulations of exosomes with distinct molecular and biological properties · 2016
    No notice
  25. 25.

    Yu X, Harris SL, Levine AJ. The regulation of exosome secretion: a novel function of the p53 protein. Cancer Res. 2006;66:4795-4801.

    Not in our library10.1158/0008-5472.can-05-4579

  26. 26.

    Bobrie A, Colombo M, Raposo G, Théry C. Exosome secretion: molecular mechanisms and roles in immune responses. Traffic. 2011;12:1659-1668.

    Not in our library10.1111/j.1600-0854.2011.01225.x

  27. 27.

    Record M, Subra C, Silvente-Poirot S, Poirot M. Exosomes as intercellular signalosomes and pharmacological effectors. Biochem Pharmacol. 2011;81:1171-1182.

    Not in our library10.1016/j.bcp.2011.02.011

  28. 28.

    Ludwig A-K, Giebel B. Exosomes: small vesicles participating in intercellular communication. Int J Biochem Cell Biol. 2012;44:11-15.

    Not in our library10.1016/j.biocel.2011.10.005

  29. 29.

    Savina A, Fader CM, Damiani MT, Colombo MI. Rab11 promotes docking and fusion of multivesicular bodies in a calcium-dependent manner. Traffic. 2005;6:131-143.

    Not in our library10.1111/j.1600-0854.2004.00257.x

  30. 30.

    Wajant H, Moosmayer D, Wüest T, Bartke T, Gerlach E, Schönherr U, Peters N, Scheurich P, Pfizenmaier K. Differential activation of TRAIL-R1 and-2 by soluble and membrane TRAIL allows selective surface antigen-directed activation of TRAIL-R2 by a soluble TRAIL derivative. Oncogene. 2001;20:4101.

    Not in our library10.1038/sj.onc.1204558

  31. 31.

    Muralidharan-Chari V, Clancy JW, Sedgwick A, D'Souza-Schorey C. Microvesicles: mediators of extracellular communication during cancer progression. J Cell Sci. 2010;123:1603-1611.

    Not in our library10.1242/jcs.064386

  32. 32.

    Cocucci E, Racchetti G, Meldolesi J. Shedding microvesicles: artefacts no more. Trends Cell Biol. 2009;19:43-51.

    Not in our library10.1016/j.tcb.2008.11.003

  33. 33.

    Saha S, Woodbine L, Haines J, Coster M, Ricket N, Barazzuol L, Ainsbury E, Sienkiewicz Z, Jeggo P. Increased apoptosis and DNA double-strand breaks in the embryonic mouse brain in response to very low-dose X-rays but not 50 Hz magnetic fields. J Royal Soc Interface. 2014;11:20140783.

    Not in our library10.1098/rsif.2014.0783

  34. 34.

    Sebbagh M, Renvoizé C, Hamelin J, Riché N, Bertoglio J, Bréard J. Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nat Cell Biol. 2001;3:346.

    Not in our library10.1038/35070019

  35. 35.

    Zhang D, Zhou T, He F, Rong Y, Lee SH, Wu S, Zuo L. Reactive oxygen species formation and bystander effects in gradient irradiation on human breast cancer cells. Oncotarget. 2016;7:41622.

    Not in our library10.18632/oncotarget.9517

  36. 36.

    van Balkom BW, Gremmels H, Giebel B, Lim SK. Proteomic signature of mesenchymal stromal cell-derived small extracellular vesicles. Proteomics. 2019;19:1800163.

    Not in our library10.1002/pmic.201800163

  37. 37.

    Schey KL, Luther JM, Rose KL. Proteomics characterization of exosome cargo. Methods. 2015;87:75-82.

    Not in our library10.1016/j.ymeth.2015.03.018

  38. 38.

    Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Bba-Gen Subjects. 1820;2012:940-948.

    Not in our library10.1016/j.bbagen.2012.03.017

  39. 39.

    Bebelman MP, Smit MJ, Pegtel DM, Baglio SR. Biogenesis and function of extracellular vesicles in cancer. Pharmacol Ther. 2018;188:1-11.

    Not in our library10.1016/j.pharmthera.2018.02.013

  40. 40.

    Schorey JS, Bhatnagar S. Exosome function: from tumor immunology to pathogen biology. Traffic. 2008;9:871-881.

    Not in our library10.1111/j.1600-0854.2008.00734.x

All 147 references

Cited by papers we hold 10

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.