Home LiteratureArticle Details
PMID: 24703619 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Extracellular vesicles: emerging targets for cancer therapy.

Trends in molecular medicine ·Vol. 20 ·No. 7 ·2014-07-00 ·Pages 385-93

Vader P, Breakefield XO, Wood MJ

Abstract

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are released by almost all cell types, including tumour cells. Through transfer of their molecular contents, EVs are capable of altering the function of recipient cells. Increasing evidence suggests a key role for EV mediated intercellular communication in a variety of cellular processes involved in tumour development and progression, including immune suppression, angiogenesis, and metastasis. Aspects of EV biogenesis or function are therefore increasingly being considered as targets for anticancer therapy. Here, we summarise the current knowledge on the contributions of EVs to cancer pathogenesis and discuss novel therapeutic strategies to target EVs to prevent tumour growth and spread.

Keywords
cancer therapy exosomes extracellular vesicles metastasis microvesicles tumour microenvironment
MeSH Terms
Animals Antineoplastic Agents/therapeutic use Cell Communication/drug effects,physiology Humans Neoplasms/drug therapy,metabolism Transport Vesicles/drug effects,physiology
Chemicals
Antineoplastic Agents
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Vader Pieter
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
Breakefield Xandra O
Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA 2129, USA.
Wood Matthew J A
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK. Electronic address: matthew.wood@dpag.ox.ac.uk.
References (88)
88 references, click to expand
  1. The genomic and proteomic content of cancer cell-derived exosomes.
    Front Oncol. 2012 Apr 17;2:38 PMID: 22649786
  2. Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR.
    Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3794-9 PMID: 19234131
  3. Activated T cells recruit exosomes secreted by dendritic cells via LFA-1.
    Blood. 2009 Feb 26;113(9):1977-81 PMID: 19064723
  4. Extracellular vesicles: exosomes, microvesicles, and friends.
    J Cell Biol. 2013 Feb 18;200(4):373-83 PMID: 23420871
  5. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response.
    Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):E2110-6 PMID: 22753494
  6. Megakaryocyte-derived microparticles: direct visualization and distinction from platelet-derived microparticles.
    Blood. 2009 Jan 29;113(5):1112-21 PMID: 18802008
  7. Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules.
    Blood. 1999 Dec 1;94(11):3791-9 PMID: 10572093
  8. Alzheimer's disease beta-amyloid peptides are released in association with exosomes.
    Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11172-7 PMID: 16837572
  9. Extracellular vesicles: biology and emerging therapeutic opportunities.
    Nat Rev Drug Discov. 2013 May;12(5):347-57 PMID: 23584393
  10. Purification, characterization and biological significance of tumor-derived exosomes.
    Anticancer Res. 2005 Nov-Dec;25(6A):3703-7 PMID: 16302729
  11. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration.
    Cell. 2012 Dec 21;151(7):1542-56 PMID: 23260141
  12. Toward tailored exosomes: the exosomal tetraspanin web contributes to target cell selection.
    Int J Biochem Cell Biol. 2012 Sep;44(9):1574-84 PMID: 22728313
  13. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers.
    Nat Cell Biol. 2008 Dec;10(12):1470-6 PMID: 19011622
  14. Rab27a supports exosome-dependent and -independent mechanisms that modify the tumor microenvironment and can promote tumor progression.
    Cancer Res. 2012 Oct 1;72(19):4920-30 PMID: 22865453
  15. MicroRNAs are exported from malignant cells in customized particles.
    Nucleic Acids Res. 2012 Oct;40(18):9125-38 PMID: 22772984
  16. Rab27 GTPases distribute extracellular nanomaps for invasive growth and metastasis: implications for prognosis and treatment.
    Int J Mol Sci. 2013 May 10;14(5):9883-92 PMID: 23665896
  17. Rab27a and Rab27b control different steps of the exosome secretion pathway.
    Nat Cell Biol. 2010 Jan;12(1):19-30; sup pp 1-13 PMID: 19966785
  18. Malignant transformation in melanocytes is associated with increased production of procoagulant microvesicles.
    Thromb Haemost. 2011 Oct;106(4):712-23 PMID: 21800005
  19. Exosomes: secreted vesicles and intercellular communications.
    F1000 Biol Rep. 2011;3:15 PMID: 21876726
  20. Exosome removal as a therapeutic adjuvant in cancer.
    J Transl Med. 2012 Jun 27;10:134 PMID: 22738135
  21. Exosome release is regulated by a calcium-dependent mechanism in K562 cells.
    J Biol Chem. 2003 May 30;278(22):20083-90 PMID: 12639953
  22. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells.
    J Clin Invest. 2010 Feb;120(2):457-71 PMID: 20093776
  23. Amedeo Avogadro's cry: what is 1 µg of exosomes?
    Bioessays. 2012 Oct;34(10):873-5 PMID: 22815202
  24. Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells.
    BMC Genomics. 2009 Nov 25;10:556 PMID: 19930720
  25. Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro.
    Blood. 2004 Nov 1;104(9):2761-6 PMID: 15242875
  26. ExoCarta 2012: database of exosomal proteins, RNA and lipids.
    Nucleic Acids Res. 2012 Jan;40(Database issue):D1241-4 PMID: 21989406
  27. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins.
    Nat Cell Biol. 2011 Apr;13(4):423-33 PMID: 21423178
  28. ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles.
    Curr Biol. 2009 Dec 1;19(22):1875-85 PMID: 19896381
  29. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming.
    Nat Med. 2001 Mar;7(3):297-303 PMID: 11231627
  30. Ceramide triggers budding of exosome vesicles into multivesicular endosomes.
    Science. 2008 Feb 29;319(5867):1244-7 PMID: 18309083
  31. Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy.
    Nat Med. 2012 Dec;18(12):1835-40 PMID: 23142818
  32. High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients.
    PLoS One. 2009;4(4):e5219 PMID: 19381331
  33. Human tumor-derived exosomes down-modulate NKG2D expression.
    J Immunol. 2008 Jun 1;180(11):7249-58 PMID: 18490724
  34. Secretory mechanisms and intercellular transfer of microRNAs in living cells.
    J Biol Chem. 2010 Jun 4;285(23):17442-52 PMID: 20353945
  35. Microenvironmental pH is a key factor for exosome traffic in tumor cells.
    J Biol Chem. 2009 Dec 4;284(49):34211-22 PMID: 19801663
  36. Exosomes containing glycoprotein 350 released by EBV-transformed B cells selectively target B cells through CD21 and block EBV infection in vitro.
    J Immunol. 2011 Jan 1;186(1):73-82 PMID: 21106852
  37. Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development.
    Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7312-7 PMID: 23589885
  38. Cancer cell-derived microvesicles induce transformation by transferring tissue transglutaminase and fibronectin to recipient cells.
    Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4852-7 PMID: 21368175
  39. Microparticle-associated tissue factor activity: a link between cancer and thrombosis?
    J Thromb Haemost. 2007 Mar;5(3):520-7 PMID: 17166244
  40. Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer.
    Int J Cancer. 2005 Feb 20;113(5):752-60 PMID: 15499615
  41. Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation.
    PLoS Biol. 2012;10(12):e1001450 PMID: 23271954
  42. Tumor angiogenesis: molecular pathways and therapeutic targets.
    Nat Med. 2011 Nov 07;17(11):1359-70 PMID: 22064426
  43. Horizontal transfer of oncogenes by uptake of apoptotic bodies.
    Proc Natl Acad Sci U S A. 2001 May 22;98(11):6407-11 PMID: 11353826
  44. Exosomes and communication between tumours and the immune system: are all exosomes equal?
    Biochem Soc Trans. 2013 Feb 1;41(1):263-7 PMID: 23356294
  45. BEAMing and Droplet Digital PCR Analysis of Mutant IDH1 mRNA in Glioma Patient Serum and Cerebrospinal Fluid Extracellular Vesicles.
    Mol Ther Nucleic Acids. 2013 Jul 23;2:e109 PMID: 23881452
  46. Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS.
    Mol Cell Proteomics. 2013 Feb;12(2):343-55 PMID: 23161513
  47. Taxol(®)-induced phosphatidylserine exposure and microvesicle formation in red blood cells is mediated by its vehicle Cremophor(®) EL.
    Nanomedicine (Lond). 2013 Jul;8(7):1127-35 PMID: 23384701
  48. Pregnancy-associated exosomes and their modulation of T cell signaling.
    J Immunol. 2006 Feb 1;176(3):1534-42 PMID: 16424182
  49. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles.
    J Cell Sci. 2013 Dec 15;126(Pt 24):5553-65 PMID: 24105262
  50. Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche.
    Cancer Res. 2011 Aug 1;71(15):5346-56 PMID: 21670082
  51. Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis.
    Blood. 2005 Feb 15;105(4):1734-41 PMID: 15494427
  52. Prediction and prevention of thromboembolic events with enoxaparin in cancer patients with elevated tissue factor-bearing microparticles: a randomized-controlled phase II trial (the Microtec study).
    Br J Haematol. 2013 Feb;160(4):530-7 PMID: 23240761
  53. Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity.
    Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17380-5 PMID: 24101524
  54. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer.
    Gynecol Oncol. 2008 Jul;110(1):13-21 PMID: 18589210
  55. Exosomal tumor microRNA modulates premetastatic organ cells.
    Neoplasia. 2013 Mar;15(3):281-95 PMID: 23479506
  56. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.
    Nat Cell Biol. 2007 Jun;9(6):654-9 PMID: 17486113
  57. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells.
    Mol Cancer. 2011 Sep 22;10:117 PMID: 21939504
  58. Paracrine induction of endothelium by tumor exosomes.
    Lab Invest. 2009 Nov;89(11):1317-28 PMID: 19786948
  59. Functional delivery of viral miRNAs via exosomes.
    Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6328-33 PMID: 20304794
  60. Classification, functions, and clinical relevance of extracellular vesicles.
    Pharmacol Rev. 2012 Jul;64(3):676-705 PMID: 22722893
  61. Exosomes as intercellular signaling organelles involved in health and disease: basic science and clinical applications.
    Int J Mol Sci. 2013 Mar 06;14(3):5338-66 PMID: 23466882
  62. Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells.
    Mol Cancer Ther. 2005 Oct;4(10):1595-604 PMID: 16227410
  63. Contribution of proteomics to understanding the role of tumor-derived exosomes in cancer progression: state of the art and new perspectives.
    Proteomics. 2013 May;13(10-11):1581-94 PMID: 23401131
  64. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery.
    Leukemia. 2006 May;20(5):847-56 PMID: 16453000
  65. Tumor-derived tissue factor activates coagulation and enhances thrombosis in a mouse xenograft model of human pancreatic cancer.
    Blood. 2012 Jun 7;119(23):5543-52 PMID: 22547577
  66. Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences.
    Nat Commun. 2011 Feb 01;2:180 PMID: 21285958
  67. Membrane vesicles as conveyors of immune responses.
    Nat Rev Immunol. 2009 Aug;9(8):581-93 PMID: 19498381
  68. Exosomal microRNA: a diagnostic marker for lung cancer.
    Clin Lung Cancer. 2009 Jan;10(1):42-6 PMID: 19289371
  69. Isolation and identification of potential urinary microparticle biomarkers of bladder cancer.
    J Proteome Res. 2008 May;7(5):2088-96 PMID: 18373357
  70. Tumour-released exosomes and their implications in cancer immunity.
    Cell Death Differ. 2008 Jan;15(1):80-8 PMID: 17932500
  71. Microvesicles as mediators of intercellular communication in cancer--the emerging science of cellular 'debris'.
    Semin Immunopathol. 2011 Sep;33(5):455-67 PMID: 21318413
  72. RhoA triggers a specific signaling pathway that generates transforming microvesicles in cancer cells.
    Oncogene. 2012 Nov 8;31(45):4740-9 PMID: 22266864
  73. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells.
    Nat Cell Biol. 2008 May;10(5):619-24 PMID: 18425114
  74. Extracellular vesicles - biomarkers and effectors of the cellular interactome in cancer.
    Front Pharmacol. 2013 Mar 06;4:21 PMID: 23508692
  75. Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles.
    Cancer Res. 2003 Aug 1;63(15):4331-7 PMID: 12907600
  76. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET.
    Nat Med. 2012 Jun;18(6):883-91 PMID: 22635005
  77. Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy.
    Clin Cancer Res. 2009 Nov 15;15(22):6830-40 PMID: 19861441
  78. Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-beta-mediated suppressive activity on T lymphocytes.
    Cancer Res. 2006 Sep 15;66(18):9290-8 PMID: 16982774
  79. Large oncosomes in human prostate cancer tissues and in the circulation of mice with metastatic disease.
    Am J Pathol. 2012 Nov;181(5):1573-84 PMID: 23022210
  80. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis.
    Cancer Res. 2011 Jun 1;71(11):3792-801 PMID: 21478294
  81. B lymphocytes secrete antigen-presenting vesicles.
    J Exp Med. 1996 Mar 1;183(3):1161-72 PMID: 8642258
  82. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research.
    J Extracell Vesicles. 2013 May 27;2: PMID: 24009894
  83. Exosomal evasion of humoral immunotherapy in aggressive B-cell lymphoma modulated by ATP-binding cassette transporter A3.
    Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15336-41 PMID: 21873242
  84. Membrane microparticles mediate transfer of P-glycoprotein to drug sensitive cancer cells.
    Leukemia. 2009 Sep;23(9):1643-9 PMID: 19369960
  85. Exosomes: extracellular organelles important in intercellular communication.
    J Proteomics. 2010 Sep 10;73(10):1907-20 PMID: 20601276
  86. Heparin blocks transfer of extracellular vesicles between donor and recipient cells.
    J Neurooncol. 2013 Dec;115(3):343-51 PMID: 24002181
  87. Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor.
    Eur J Cancer. 2003 Jan;39(2):184-91 PMID: 12509950
  88. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles.
    J Immunol. 2001 Jun 15;166(12):7309-18 PMID: 11390481
Article Info
Journal
Trends in molecular medicine
Abbr.
Trends Mol Med
ISSN
1471-499X
DOI
10.1016/j.molmed.2014.03.002
Email
matthew.wood@dpag.ox.ac.uk
Published
2014-07-00
Epub
2014-00-03
Pages
385-93
Language
English
Region
England
NLM ID
100966035
PMCID
PMC4082760
Subset
IM
Grants
Parkinson's UK · G-1109 · United Kingdom
NCI NIH HHS · U19 CA179563 · United States
NCI NIH HHS · CA179563 · United States
External Links
PubMed source DOI: 10.1016/j.molmed.2014.03.002 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2