Skip to main content

EV, Microvesicles/MicroRNAs and Stem Cells in Cancer

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1056))

Abstract

The role of extracellular vesicles (EV) in carcinogenesis has become the focus of much research. These microscopic messengers have been found to regulate immune system function, particularly in tumorigenesis, as well as conditioning future metastatic sites for the attachment and growth of tumor tissue. Through an interaction with a range of host tissues, EVs are able to generate a pro-tumor environment that is essential for tumorigenesis. These small nanovesicles are an ideal candidate for a non-invasive indicator of pathogenesis and/or disease progression as they can display individualized nucleic acid, protein, and lipid expression profiles that are often reflective of disease state, and can be easily detected in bodily fluids, even after extended cryo-storage. Furthermore, the ability of EVs to securely transport signaling molecules and localize to distant tissues suggests these particles may greatly improve the delivery of therapeutic treatments, particularly in cancer. In this chapter, we discuss the role of EV in the identification of new diagnostic and prognostic cancer biomarkers, as well as the development of novel EV-based cancer therapies.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Haber DA, Velculescu VE (2014) Blood-based analyses of cancer: circulating tumor cells and circulating tumor DNA. Cancer Discov 4(6):650–661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Webb S (2016) The cancer bloodhounds. Nat Biotechnol 34(11):1090–1094

    Article  CAS  PubMed  Google Scholar 

  3. Henderson MC, Azorsa DO (2012) The genomic and proteomic content of cancer cell-derived exosomes. Front Oncol 2:1–9

    Article  Google Scholar 

  4. Brock G, Castellanos-Rizaldos E, Hu L, Coticchia C, Skog J (2015) Liquid biopsy for cancer screening, patient stratification and monitoring. Transl Cancer Res 4(3):280–290

    CAS  Google Scholar 

  5. Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, Dingli F, Loew D, Tkach M, Thery C (2016) Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci 113(8):E968–E977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Thery C, Amigorena S, Raposo G, Clayton A (2006) Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol Chapter 3(Unit 3):22

    PubMed  Google Scholar 

  7. Witwer KW, Buzas EI, Bemis LT, Bora A, Lasser C, Lotvall J, Nolte-’t Hoen EN, Piper MG, Sivaraman S, Skog J, Thery C, Wauben MH, Hochberg F (2013) Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles 2. https://doi.org/10.3402/jev.v2i0.20360

  8. Johnsen KB, Gudbergsson JM, Skov MN, Pilgaard L, Moos T, Duroux M (2014) A comprehensive overview of exosomes as drug delivery vehicles—endogenous nanocarriers for targeted cancer therapy. Biochim Biophys Acta 1846(1):75–87

    CAS  PubMed  Google Scholar 

  9. Zeringer E, Barta T, Li M, Vlassov AV (2015) Strategies for isolation of exosomes. Cold Spring Harb Protoc 2015(4):pdb.top074476

    Article  Google Scholar 

  10. Simpson RJ, Lim JW, Moritz RL, Mathivanan S (2009) Exosomes: proteomic insights and diagnostic potential. Expert Rev Proteomics 6(3):267–283

    Article  CAS  PubMed  Google Scholar 

  11. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435(7043):834–838

    Article  CAS  PubMed  Google Scholar 

  12. Cappello F, Logozzi M, Campanella C, Bavisotto CC, Marcilla A, Properzi F, Fais S (2017) Exosome levels in human body fluids: a tumor marker by themselves? Eur J Pharm Sci 96:93–98

    Article  CAS  PubMed  Google Scholar 

  13. Gusachenko ON, Zenkova MA, Vlassov VV (2013) Nucleic acids in exosomes: disease markers and intercellular communication molecules. Biochemistry (Mosc) 78(1):1–7

    Article  CAS  Google Scholar 

  14. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci 105(30):10513–10518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Raponi M, Dossey L, Jatkoe T, Wu X, Chen G, Fan H, Beer DG (2009) MicroRNA classifiers for predicting prognosis of squamous cell lung cancer. Cancer Res 69(14):5776–5783

    Article  CAS  PubMed  Google Scholar 

  16. Wu M, Jolicoeur N, Li Z, Zhang L, Fortin Y, L’Abbe D, Yu Z, Shen SH (2008) Genetic variations of microRNAs in human cancer and their effects on the expression of miRNAs. Carcinogenesis 29(9):1710–1716

    Article  CAS  PubMed  Google Scholar 

  17. Zheng D, Haddadin S, Wang Y, Gu L-Q, Perry MC, Freter CE, Wang MX (2011) Plasma microRNAs as novel biomarkers for early detection of lung cancer. Int J Clin Exp Pathol 4(6):575–586

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Kosaka N, Iguchi H, Ochiya T (2010) Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci 101(10):2087–2092

    Article  CAS  PubMed  Google Scholar 

  19. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659

    Article  CAS  PubMed  Google Scholar 

  20. Thakur BK, Zhang H, Becker A, Matei I, Huang Y, Costa-Silva B, Zheng Y, Hoshino A, Brazier H, Xiang 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(6):766–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Curry WT, Carter BS, Krichevsky AM, Breakefield XO (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10(12):1470–1476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 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

    Article  PubMed  CAS  Google Scholar 

  23. Kahlert C, Melo SA, Protopopov A, Tang J, Seth S, Koch M, Zhang J, Weitz J, Chin L, Futreal A, Kalluri R (2014) Identification of double stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer. J Biol Chem 289(7):3869–3875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Li Y, Zheng Q, Bao C, Li S, Guo W, Zhao J, Chen D, Gu J, He X, Huang S (2015) Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res 25(8):981–984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Miranda KC, Bond DT, McKee M, Skog J, Paunescu TG, Da Silva N, Brown D, Russo LM (2010) Nucleic acids within urinary exosomes/microvesicles are potential biomarkers for renal disease. Kidney Int 78(2):191–199

    Article  PubMed  PubMed Central  Google Scholar 

  26. Duijvesz D, Burnum-Johnson KE, Gritsenko MA, Hoogland AM, Vredenbregt-van den Berg MS, Willemsen R, Luider T, Pasa-Tolic L, Jenster G (2013) Proteomic profiling of exosomes leads to the identification of novel biomarkers for prostate cancer. PLoS One 8(12):e82589

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Duijvesz D, Luider T, Bangma CH, Jenster G (2011) Exosomes as biomarker treasure chests for prostate cancer. Eur Urol 59(5):823–831

    Article  CAS  PubMed  Google Scholar 

  28. Jakobsen KR, Paulsen BS, Baek R, Varming K, Sorensen BS, Jorgensen MM (2015) Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma. J Extracell Vesicles 4:26659

    Article  PubMed  CAS  Google Scholar 

  29. 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(7559):177–182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Llorente A, Skotland T, Sylvanne T, Kauhanen D, Rog T, Orlowski A, Vattulainen I, Ekroos K, Sandvig K (2013) Molecular lipidomics of exosomes released by PC-3 prostate cancer cells. Biochim Biophys Acta 1831(7):1302–1309

    Article  CAS  PubMed  Google Scholar 

  31. Ko J, Carpenter E, Issadore D (2016) Detection and isolation of circulating exosomes and microvesicles for cancer monitoring and diagnostics using micro-/nano-based devices. Analyst 141(2):450–460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. 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(11):1891–1900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 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(3):489–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. 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. Nat Commun 5:3591

    Article  PubMed  CAS  Google Scholar 

  35. Noerholm M, Balaj L, Limperg T, Salehi A, Zhu LD, Hochberg FH, Breakefield XO, Carter BS, Skog J (2012) RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls. BMC Cancer 12:22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Shao H, Chung J, Lee K, Balaj L, Min C, Carter BS, Hochberg FH, Breakefield XO, Lee H, Weissleder R (2015) Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma. Nat Commun 6:6999

    Article  CAS  PubMed  Google Scholar 

  37. Goda T, Masuno K, Nishida J, Kosaka N, Ochiya T, Matsumoto A, Miyahara Y (2012) A label-free electrical detection of exosomal microRNAs using microelectrode array. Chem Commun 48(98):11942–11944

    Article  CAS  Google Scholar 

  38. Tavoosidana G, Ronquist G, Darmanis S, Yan J, Carlsson L, Wu D, Conze T, Ek P, Semjonow A, Eltze E, Larsson A, Landegren UD, Kamali-Moghaddam M (2011) Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer. Proc Natl Acad Sci 108(21):8809–8814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE (2009) The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol 112(1):55–59

    Article  CAS  PubMed  Google Scholar 

  40. Shao H, Chung J, Balaj L, Charest A, Bigner DD, Carter BS, Hochberg FH, Breakefield XO, Weissleder R, Lee H (2012) Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy. Nat Med 18(12):1835–1840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Jeong S, Park J, Pathania D, Castro CM, Weissleder R, Lee H (2016) Integrated magneto-electrochemical sensor for exosome analysis. ACS Nano 10(2):1802–1809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Enderle D, Spiel A, Coticchia CM, Berghoff E, Mueller R, Schlumpberger M, Sprenger-Haussels M, Shaffer JM, Lader E, Skog J, Noerholm M (2015) Characterization of RNA from exosomes and other extracellular vesicles isolated by a novel spin column-based method. PLoS One 10(8):e0136133

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Donovan MJ, Noerholm M, Bentink S, Belzer S, Skog J, O’Neill V, Cochran JS, Brown GA (2015) A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result. Prostate Cancer Prostatic Dis 18(4):370–375

    Article  CAS  PubMed  Google Scholar 

  44. Vlassov AV, Magdaleno S, Setterquist R, Conrad R (2012) Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 1820(7):940–948

    Article  CAS  PubMed  Google Scholar 

  45. el-Andaloussi S, Mager I, Breakefield XO, Wood MJ (2013) Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov 12(5):347–357

    Article  CAS  PubMed  Google Scholar 

  46. Thery C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2(8):569–579

    Article  CAS  PubMed  Google Scholar 

  47. Kharaziha P, Ceder S, Li Q, Panaretakis T (2012) Tumor cell-derived exosomes: a message in a bottle. Biochim Biophys Acta 1826(1):103–111

    CAS  PubMed  Google Scholar 

  48. Tickner JA, Urquhart AJ, Stephenson S-A, Richard DJ, O’Byrne KJ (2014) Functions and Therapeutic Roles of Exosomes in Cancer. Front Oncol 4:127

    Article  PubMed  PubMed Central  Google Scholar 

  49. Kotmakci M, Bozok Cetintas V (2015) Extracellular vesicles as natural nanosized delivery systems for small-molecule drugs and genetic material: steps towards the future nanomedicines. J Pharm Pharm Sci 18(3):396–413

    Article  CAS  PubMed  Google Scholar 

  50. Smyth T, Kullberg M, Malik N, Smith-Jones P, Graner MW, Anchordoquy TJ (2015) Biodistribution and delivery efficiency of unmodified tumor-derived exosomes. J Control Release 199:145–155

    Article  CAS  PubMed  Google Scholar 

  51. Ha D, Yang N, Nadithe V (2016) Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges. Acta Pharm Sin B 6(4):287–296

    Article  PubMed  PubMed Central  Google Scholar 

  52. Maguire CA, Balaj L, Sivaraman S, Crommentuijn MH, Ericsson M, Mincheva-Nilsson L, Baranov V, Gianni D, Tannous BA, Sena-Esteves M, Breakefield XO, Skog J (2012) Microvesicle-associated AAV vector as a novel gene delivery system. Mol Ther 20(5):960–971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ohno S, Takanashi M, Sudo K, Ueda S, Ishikawa A, Matsuyama N, Fujita K, Mizutani T, Ohgi T, Ochiya T, Gotoh N, Kuroda M (2013) Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther 21(1):185–191

    Article  CAS  PubMed  Google Scholar 

  54. Mizrak A, Bolukbasi MF, Ozdener GB, Brenner GJ, Madlener S, Erkan EP, Strobel T, Breakefield XO, Saydam O (2013) Genetically engineered microvesicles carrying suicide mRNA/protein inhibit schwannoma tumor growth. Mol Ther 21(1):101–108

    Article  CAS  PubMed  Google Scholar 

  55. Lee YS, Kim SH, Cho JA, Kim CW (2011) Introduction of the CIITA gene into tumor cells produces exosomes with enhanced anti-tumor effects. Exp Mol Med 43(5):281–290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ (2011) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29(4):341–345

    Article  CAS  PubMed  Google Scholar 

  57. Yang T, Martin P, Fogarty B, Brown A, Schurman K, Phipps R, Yin VP, Lockman P, Bai S (2015) Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio. Pharm Res 32(6):2003–2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Tian Y, Li S, Song J, Ji T, Zhu M, Anderson GJ, Wei J, Nie G (2014) A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials 35(7):2383–2390

    Article  CAS  PubMed  Google Scholar 

  59. Kim MS, Haney MJ, Zhao Y, Mahajan V, Deygen I, Klyachko NL, Inskoe E, Piroyan A, Sokolsky M, Okolie O, Hingtgen SD, Kabanov AV, Batrakova EV (2016) Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine 12(3):655–664

    Article  CAS  PubMed  Google Scholar 

  60. Pascucci L, Cocce V, Bonomi A, Ami D, Ceccarelli P, Ciusani E, Vigano L, Locatelli A, Sisto F, Doglia SM, Parati E, Bernardo ME, Muraca M, Alessandri G, Bondiolotti G, Pessina A (2014) Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: a new approach for drug delivery. J Control Release 192:262–270

    Article  CAS  PubMed  Google Scholar 

  61. Saari H, Lazaro-Ibanez E, Viitala T, Vuorimaa-Laukkanen E, Siljander P, Yliperttula M (2015) Microvesicle- and exosome-mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells. J Control Release 220(Pt B):727–737

    Article  CAS  PubMed  Google Scholar 

  62. Fuhrmann G, Serio A, Mazo M, Nair R, Stevens MM (2015) Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins. J Control Release 205:35–44

    Article  CAS  PubMed  Google Scholar 

  63. Katakowski M, Zheng X, Jiang F, Rogers T, Szalad A, Chopp M (2010) MiR-146b-5p suppresses EGFR expression and reduces in vitro migration and invasion of glioma. Cancer Invest 28(10):1024–1030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Katakowski M, Buller B, Zheng X, Lu Y, Rogers T, Osobamiro O, Shu W, Jiang F, Chopp M (2013) Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett 335(1):201–204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Munoz JL, Bliss SA, Greco SJ, Ramkissoon SH, Ligon KL, Rameshwar P (2013) Delivery of functional anti-mir-9 by mesenchymal stem cell-derived exosomes to glioblastoma multiforme cells conferred chemosensitivity. Mol Ther Nucleic Acids 2:e126

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Bruno S, Collino F, Deregibus MC, Grange C, Tetta C, Camussi G (2013) Microvesicles derived from human bone marrow mesenchymal stem cells inhibit tumor growth. Stem Cells Dev 22(5):758–771

    Article  CAS  PubMed  Google Scholar 

  67. Kooijmans SA, Vader P, van Dommelen SM, van Solinge WW, Schiffelers RM (2012) Exosome mimetics: a novel class of drug delivery systems. Int J Nanomedicine 7:1525–1541

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Jang SC, Kim OY, Yoon CM, Choi DS, Roh TY, Park J, Nilsson J, Lotvall J, Kim YK, Gho YS (2013) Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. ACS Nano 7(9):7698–7710

    Article  CAS  PubMed  Google Scholar 

  69. Gobbo J, Marcion G, Cordonnier M, Dias AM, Pernet N, Hammann A, Richaud S, Mjahed H, Isambert N, Clausse V, Rebe C, Bertaut A, Goussot V, Lirussi F, Ghiringhelli F, de Thonel A, Fumoleau P, Seigneuric R, Garrido C (2016) Restoring anticancer immune response by targeting tumor-derived exosomes with a HSP70 peptide aptamer. J Natl Cancer Inst 108(3)

    Article  CAS  Google Scholar 

  70. Alderton GK (2012) Metastasis: exosomes drive premetastatic niche formation. Nat Rev Cancer 12(7):447. https://doi.org/10.1038/nrc3304

    Article  CAS  PubMed  Google Scholar 

  71. Psaila B, Lyden D (2009) The metastatic niche: adapting the foreign soil. Nat Rev Cancer 9(4):285–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Sceneay J, Smyth MJ, Moller A (2013) The pre-metastatic niche: finding common ground. Cancer Metastasis Rev 32(3-4):449–464. https://doi.org/10.1007/s10555-013-9420-1

    Article  CAS  PubMed  Google Scholar 

  73. Ciravolo V, Huber V, Ghedini GC, Venturelli E, Bianchi F, Campiglio M, Morelli D, Villa A, Della Mina P, Menard S, Filipazzi P, Rivoltini L, Tagliabue E, Pupa SM (2012) Potential role of HER2-overexpressing exosomes in countering trastuzumab-based therapy. J Cell Physiol 227(2):658–667

    Article  CAS  PubMed  Google Scholar 

  74. Corcoran C, Rani S, O’Brien K, O’Neill A, Prencipe M, Sheikh R, Webb G, McDermott R, Watson W, Crown J, O’Driscoll L (2012) Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes. PLoS One 7(12):e50999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Bobrie A, Krumeich S, Reyal F, Recchi C, Moita LF, Seabra MC, Ostrowski M, Thery C (2012) Rab27a supports exosome-dependent and -independent mechanisms that modify the tumor microenvironment and can promote tumor progression. Cancer Res 72(19):4920–4930

    Article  CAS  PubMed  Google Scholar 

  76. Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, Schwille P, Brugger B, Simons M (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319(5867):1244–1247

    Article  CAS  PubMed  Google Scholar 

  77. Peinado H, cacute MsaAck, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, a-Santos GGi, Ghajar CM, Nitadori-Hoshino A, Hoffman C, Badal K, Garcia BA, Callahan MK, Yuan J, Martins VR, Skog J, Kaplan RN, Brady MS, Wolchok JD, Bromberg J, Lyden D, Chapman PB, Kang Y (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18(6):883–891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Marleau AM, Chen CS, Joyce JA, Tullis RH (2012) Exosome removal as a therapeutic adjuvant in cancer. J Transl Med 10:134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Mignot G, Roux S, Thery C, Ségura E, Zitvogel L (2006) Prospects for exosomes in immunotherapy of cancer. J Cell Mol Med 10(2):376–388

    Article  CAS  PubMed  Google Scholar 

  80. Escudier B, Dorval T, Chaput N, André F, Caby M-P, Novault S, Flament C, Leboulaire C, Borg C, Amigorena S, Boccaccio C, Bonnerot C, Dhellin O, Movassagh M, Piperno S, Robert C, Serra V, Valente N, Le Pecq J-B, Spatz A, Lantz O, Tursz T, Angevin E, Zitvogel L (2005) Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial. J Transl Med 3(1):1–13

    Article  CAS  Google Scholar 

  81. Dai S, Wei D, Wu Z, Zhou X, Wei X, Huang H, Li G (2008) Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer. Mol Ther 16(4):782–790

    Article  CAS  PubMed  Google Scholar 

  82. Stremersch S, Vandenbroucke RE, Van Wonterghem E, Hendrix A, De Smedt SC, Raemdonck K (2016) Comparing exosome-like vesicles with liposomes for the functional cellular delivery of small RNAs. J Control Release 232:51–61

    Article  CAS  PubMed  Google Scholar 

  83. Karanth H, Murthy RS (2007) pH-sensitive liposomes—principle and application in cancer therapy. J Pharm Pharmacol 59(4):469–483

    Article  CAS  PubMed  Google Scholar 

  84. Mortensen JH, Jeppesen M, Pilgaard L, Agger R, Duroux M, Zachar V, Moos T (2013) Targeted antiepidermal growth factor receptor (cetuximab) immunoliposomes enhance cellular uptake in vitro and exhibit increased accumulation in an intracranial model of glioblastoma multiforme. J Drug Deliv 2013:209205

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Delcayre A, Estelles A, Sperinde J, Roulon T, Paz P, Aguilar B, Villanueva J, Khine S, Le Pecq JB (2005) Exosome display technology: applications to the development of new diagnostics and therapeutics. Blood Cells Mol Dis 35(2):158–168

    Article  CAS  PubMed  Google Scholar 

  86. Federici C, Petrucci F, Caimi S, Cesolini A, Logozzi M, Borghi M, D’Ilio S, Lugini L, Violante N, Azzarito T, Majorani C, Brambilla D, Fais S (2014) Exosome release and low pH belong to a framework of resistance of human melanoma cells to cisplatin. PLoS One 9(2):e88193

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Yang XZ, Dou S, Sun TM, Mao CQ, Wang HX, Wang J (2011) Systemic delivery of siRNA with cationic lipid assisted PEG-PLA nanoparticles for cancer therapy. J Control Release 156(2):203–211

    Article  CAS  PubMed  Google Scholar 

  88. Moore C, Kosgodage U, Lange S, Inal JM (2017) The emerging role of exosome and microvesicle- (EMV-) based cancer therapeutics and immunotherapy. 141(3):428–436. https://doi.org/10.1002/ijc.30672

  89. Rountree RB, Mandl SJ, Nachtwey JM, Dalpozzo K, Do L, Lombardo JR, Schoonmaker PL, Brinkmann K, Dirmeier U, Laus R, Delcayre A (2011) Exosome targeting of tumor antigens expressed by cancer vaccines can improve antigen immunogenicity and therapeutic efficacy. Cancer Res 71(15):5235–5244

    Article  CAS  PubMed  Google Scholar 

  90. Clayton A, Mason MD (2009) Exosomes in tumour immunity. Curr Oncol 16(3):46–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Rana S, Yue S, Stadel D, Zoller M (2012) Toward tailored exosomes: the exosomal tetraspanin web contributes to target cell selection. Int J Biochem Cell Biol 44(9):1574–1584

    Article  CAS  PubMed  Google Scholar 

  92. Viaud S, Thery C, Ploix S, Tursz T, Lapierre V, Lantz O, Zitvogel L, Chaput N (2010) Dendritic cell-derived exosomes for cancer immunotherapy: what’s next? Cancer Res 70(4):1281–1285

    Article  CAS  PubMed  Google Scholar 

  93. Chaput N, Taieb J, Andre F, Zitvogel L (2005) The potential of exosomes in immunotherapy. Expert Opin Biol Ther 5(6):737–747

    Article  CAS  PubMed  Google Scholar 

  94. Zeelenberg IS, Ostrowski M, Krumeich S, Bobrie A, Jancic C, Boissonnas A, Delcayre A, Le Pecq JB, Combadiere B, Amigorena S, Thery C (2008) Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses. Cancer Res 68(4):1228–1235

    Article  CAS  PubMed  Google Scholar 

  95. Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, Ricciardi-Castagnoli P, Raposo G, Amigorena S (1998) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med 4(5):594–600

    Article  CAS  PubMed  Google Scholar 

  96. Thery C, Ostrowski M, Segura E (2009) Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9(8):581–593

    Article  CAS  PubMed  Google Scholar 

  97. Morse MA, Garst J, Osada T, Khan S, Hobeika A, Clay TM, Valente N, Shreeniwas R, Sutton M, Delcayre A, Hsu D-H, Le Pecq J-B, Lyerly HK (2005) A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J Transl Med 3(1):9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Phinney DG, Pittenger MF (2017) Concise review: MSC-derived exosomes for cell-free therapy. Stem Cells 35(4):851–858

    Article  CAS  PubMed  Google Scholar 

  99. Yeo RW, Lai RC, Zhang B, Tan SS, Yin Y, Teh BJ, Lim SK (2013) Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery. Adv Drug Deliv Rev 65(3):336–341

    Article  CAS  PubMed  Google Scholar 

  100. Chen TS, Arslan F, Yin Y, Tan SS, Lai RC, Choo ABH, Padmanabhan J, Lee CN, de Kleijn DPV, Lim SK (2011) Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs. J Transl Med 9:47–47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Schirmaier C, Jossen V, Kaiser SC, Jüngerkes F, Brill S, Safavi-Nab A, Siehoff A, van den Bos C, Eibl D, Eibl R (2014) Scale-up of adipose tissue-derived mesenchymal stem cell production in stirred single-use bioreactors under low-serum conditions. Eng Life Sci 14(3):292–303

    Article  CAS  Google Scholar 

  102. Munagala R, Aqil F, Jeyabalan J, Gupta RC (2016) Bovine milk-derived exosomes for drug delivery. Cancer Lett 371(1):48–61

    Article  CAS  PubMed  Google Scholar 

  103. Shtam TA, Kovalev RA, Varfolomeeva EY, Makarov EM, Kil YV, Filatov MV (2013) Exosomes are natural carriers of exogenous siRNA to human cells in vitro. Cell Commun Signal 11(1):88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Besse B, Charrier M, Lapierre V, Dansin E, Lantz O, Planchard D, Le Chevalier T, Livartoski A, Barlesi F, Laplanche A, Ploix S, Vimond N, Peguillet I, Thery C, Lacroix L, Zoernig I, Dhodapkar K, Dhodapkar M, Viaud S, Soria JC, Reiners KS, Pogge von Strandmann E, Vely F, Rusakiewicz S, Eggermont A, Pitt JM, Zitvogel L, Chaput N (2016) Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. Oncoimmunology 5(4):e1071008

    Article  PubMed  CAS  Google Scholar 

  105. Chaput N, Schartz NE, Andre F, Taieb J, Novault S, Bonnaventure P, Aubert N, Bernard J, Lemonnier F, Merad M, Adema G, Adams M, Ferrantini M, Carpentier AF, Escudier B, Tursz T, Angevin E, Zitvogel L (2004) Exosomes as potent cell-free peptide-based vaccine. II. Exosomes in CpG adjuvants efficiently prime naive Tc1 lymphocytes leading to tumor rejection. J Immunol 172(4):2137–2146

    Article  CAS  PubMed  Google Scholar 

  106. Yang Y, Xiu F, Cai Z, Wang J, Wang Q, Fu Y, Cao X (2007) Increased induction of antitumor response by exosomes derived from interleukin-2 gene-modified tumor cells. J Cancer Res Clin Oncol 133(6):389–399

    Article  PubMed  Google Scholar 

  107. Harshyne LA, Hooper KM, Andrews EG, Nasca BJ, Kenyon LC, Andrews DW, Hooper DC (2015) Glioblastoma exosomes and IGF-1R/AS-ODN are immunogenic stimuli in a translational research immunotherapy paradigm. Cancer Immunol Immunother 64(3):299–309

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kenneth J. O’Byrne .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Tickner, J.A., Richard, D.J., O’Byrne, K.J. (2018). EV, Microvesicles/MicroRNAs and Stem Cells in Cancer. In: Mettinger, K., Rameshwar, P., Kumar, V. (eds) Exosomes, Stem Cells and MicroRNA. Advances in Experimental Medicine and Biology, vol 1056. Springer, Cham. https://doi.org/10.1007/978-3-319-74470-4_8

Download citation

Publish with us

Policies and ethics