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Exosomes Derived from Breast Cancer Cells, Small Trojan Horses?

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Exosomes are small extracellular vesicles secreted to the extracellular environment by several cell types, including tumor cells. It has been demonstrated that exosomes have an important role in intercellular communication, but they have recently been implicated in various tumor processes, including the oncogenic transformation of cells in the tumor microenvironment, tumor drug resistance, and the transport of tumor factors. Tumors appear to use exosomes to dialogue with and transform neighboring cells to create an ideal environment for their growth and expansion. On the other hand, the structure and function of exosomes may make them useful in cancer diagnosis and prognosis, because they contain molecules that could serve as biomarkers, including oncogenes, miRNAs, and certain proteins. They have the ability to travel via body fluids, from which they could be isolated and used to transport drugs to specific targets. This review aims to provide an update on the role of exosomes derived from breast cancer cells.

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Abbreviations

ADSC:

Adipose tissue-derived stem cells

AREG:

Amphiregulin

CAF:

Cancer-associated fibroblasts

CCL5:

Chemokine (C-C motif) ligand 5

CD:

Cluster differentiation

CTC:

Circulating tumor cells

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

EpCAM:

Epithelial cellular adhesion molecule

ERK:

Extracellular-signal-regulated kinase

FAK:

Focal adhesion kinase

FN:

Fibronectin

HB-EGF:

Heparin-binding epidermal growth factor

HER2:

Human epidermal growth factor receptor type 2

HGF:

Hepatocyte growth factor

HIF:

Hypoxia-inducible factor

HLA:

Human leukocyte antigen

HRG:

Heregulin

HSP:

Heat shock proteins

hTERT:

Human telomerase reverse transcriptase

MAC:

Membrane attack complex

MDR:

Multidrug resistance

MVB:

Multivesicular body

PBS:

Phosphate-buffered saline

PCP:

Planar cellular polarity

SDF:

Stromal cell-derived factor

TGF:

Transforming growth factor

tTG:

Tissue transglutaminase

VEGF:

Vascular endothelial growth factor

References

  1. Malvezzi M, Bertuccio P, Levi F, La Vecchia C, Negri E. European cancer mortality predictions for the year 2014. Ann Oncol. 2014;25(8):1650–6.

    Article  CAS  PubMed  Google Scholar 

  2. Carrasco E, Alvarez PJ, Prados J, Melguizo C, Rama AR, Aránega A, et al. Cancer stem cells and their implication in breast cancer. Eur J Clin Investig. 2014;44(7):678–87.

    Article  CAS  Google Scholar 

  3. Boyle ST, Kochetkova M. Breast cancer stem cells and the immune system: promotion, evasion and therapy. J Mammary Gland Biol Neoplasia. 2014;19(2):203–11.

    Article  PubMed  Google Scholar 

  4. Ogorevc E, Kralj-Iglic V, Veranic P. The role of extracellular vesicles in phenotypic cancer transformation. Radiol Oncol. 2013;47(3):197–205.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Pisitkun T, Shen R-F, Knepper MA. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci. 2004;101(36):13368–73.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Graves LE, Ariztia EV, Navari JR, Matzel HJ, Stack MS, Fishman DA. Proinvasive properties of ovarian cancer Ascites-derived membrane vesicles. Cancer Res. 2004;64(19):7045–9.

    Article  CAS  PubMed  Google Scholar 

  7. Kim HK, Song KS, Park YS, Kang YH, Lee YJ, Lee KR, et al. 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;39(2):184–91.

    Article  CAS  PubMed  Google Scholar 

  8. Baran J, Baj-Krzyworzeka M, Weglarczyk K, Szatanek R, Zembala M, Barbasz J, et al. Circulating tumour-derived microvesicles in plasma of gastric cancer patients. Cancer Immunol Immunother. 2010;59(6):841–50.

    Article  CAS  PubMed  Google Scholar 

  9. Pant S, Hilton H, Burczynski ME. The multifaceted exosome: biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities. Biochem Pharmacol. 2012;83(11):1484–94.

    Article  CAS  PubMed  Google Scholar 

  10. Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta. 2012;1820(7):940–8.

    Article  CAS  PubMed  Google Scholar 

  11. Keller S, Sanderson MP, Stoeck A, Altevogt P. Exosomes: from biogenesis and secretion to biological function. Immunol Lett. 2006;107(2):102–8.

    Article  CAS  PubMed  Google Scholar 

  12. Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2(8):569–79.

    PubMed  Google Scholar 

  13. Andre F, Schartz NE, Movassagh M, Flament C, Pautier P, Morice P, et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet. 2002;360(9329):295–305.

    Article  CAS  PubMed  Google Scholar 

  14. Hendrix A, Westbroek W, Bracke M, Wever OD. An Ex(o)citing machinery for invasive tumor growth. Cancer Res. 2010;70(23):9533–7.

    Article  CAS  PubMed  Google Scholar 

  15. Simons M, Raposo G. Exosomes – vesicular carriers for intercellular communication. Curr Opin Cell Biol. 2009;21(4):575–81.

    Article  CAS  PubMed  Google Scholar 

  16. Choi D-S, Kim D-K, Kim Y-K, Gho YS. Proteomics of extracellular vesicles: exosomes and ectosomes. Mass Spectrom Rev. 2015;34(4):474–90.

  17. Kalra H, Simpson RJ, Ji H, Aikawa E, Altevogt P, Askenase P, et al. Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLoS Biol. 2012;10(12):e1001450.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication. J Proteomics. 2010;73(10):1907–20.

    Article  CAS  PubMed  Google Scholar 

  19. Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9(8):581–93.

    Article  PubMed  Google Scholar 

  20. Luga V, Zhang L, Viloria-Petit AM, Ogunjimi AA, Inanlou MR, Chiu E, et al. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell. 2012;151(7):1542–56.

    Article  CAS  PubMed  Google Scholar 

  21. Balaj L, Lessard R, Dai L, Cho Y-J, Pomeroy SL, Breakefield XO, et al. Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat Commun. 2011;2:180.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Mathivanan S, Fahner CJ, Reid GE, Simpson RJ. ExoCarta 2012: database of exosomal proteins. RNA Lipids Nucleic Acids Res. 2012;40(D1):D1241–4.

    Article  CAS  PubMed  Google Scholar 

  23. Rak J, Guha A. Extracellular vesicles--vehicles that spread cancer genes. BioEssays. 2012;34(6):489–97.

    Article  CAS  PubMed  Google Scholar 

  24. Wendler F, Bota-Rabassedas N, Franch-Marro X. Cancer becomes wasteful: emerging roles of exosomes in cell-fate determination. J Extracell Vesicles. 2013;2:22390.

    Article  Google Scholar 

  25. Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L, Guha A, et al. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol. 2008;10(5):619–24.

    Article  CAS  PubMed  Google Scholar 

  26. Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Curry WT, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10(12):1470–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Janowska-Wieczorek A, Marquez-Curtis LA, Wysoczynski M, Ratajczak MZ. Enhancing effect of platelet-derived microvesicles on the invasive potential of breast cancer cells. Transfusion. 2006;46(7):1199–209.

    Article  PubMed  Google Scholar 

  28. Antonyak MA, Li B, Boroughs LK, Johnson JL, Druso JE, Bryant KL, et al. Cancer cell-derived microvesicles induce transformation by transferring tissue transglutaminase and fibronectin to recipient cells. Proc Natl Acad Sci. 2011;108(12):4852–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Cho JA, Park H, Lim EH, Lee KW. Exosomes from breast cancer cells can convert adipose tissue-derived mesenchymal stem cells into myofibroblast-like cells. Int J Oncol. 2012;40(1):130–8.

    CAS  PubMed  Google Scholar 

  30. O’Brien K, Rani S, Corcoran C, Wallace R, Hughes L, Friel AM, et al. Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells. Eur J Cancer. 2013;49(8):1845–59.

    Article  PubMed  Google Scholar 

  31. Higginbotham JN, Beckler MD, Gephart JD, Franklin JL, Bogatcheva G, Kremers G-J, et al. Amphiregulin exosomes increase cancer cell invasion. Curr Biol. 2011;21(9):779–86.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Dolo V, Ginestra A, Cassarà D, Violini S, Lucania G, Torrisi MR, et al. Selective localization of matrix metalloproteinase 9, beta1 integrins, and human lymphocyte antigen class I molecules on membrane vesicles shed by 8701-BC breast carcinoma cells. Cancer Res. 1998;58(19):4468–74.

    CAS  PubMed  Google Scholar 

  33. Friel AM, Corcoran C, Crown J, O’Driscoll L. Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer. Breast Cancer Res Treat. 2010;123(3):613–25.

    Article  CAS  PubMed  Google Scholar 

  34. Rupp A-K, Rupp C, Keller S, Brase JC, Ehehalt R, Fogel M, et al. Loss of EpCAM expression in breast cancer derived serum exosomes: role of proteolytic cleavage. Gynecol Oncol. 2011;122(2):437–46.

    Article  CAS  PubMed  Google Scholar 

  35. Palazzolo G, Albanese NN, Cara GD, Gygax D, Vittorelli ML, Pucci-Minafra I. Proteomic analysis of exosome-like vesicles derived from breast cancer cells. Anticancer Res. 2012;32(3):847–60.

    CAS  PubMed  Google Scholar 

  36. Kruger S, Elmageed ZY, Hawke DH, Wörner PM, Jansen DA, Abdel-Mageed AB, et al. Molecular characterization of exosome-like vesicles from breast cancer cells. BMC Cancer. 2014;14:44.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Lau CS, Wong DTW. Breast cancer exosome-like microvesicles and salivary gland cells interplay alters salivary gland cell-derived exosome-like microvesicles in vitro. PLoS ONE. 2012;7(3):e33037.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Staubach S, Razawi H, Hanisch F-G. Proteomics of MUC1-containing lipid rafts from plasma membranes and exosomes of human breast carcinoma cells MCF-7. Proteomics. 2009;9(10):2820–35.

    Article  CAS  PubMed  Google Scholar 

  39. Carrasco E, Álvarez PJ, Melguizo C, Prados J, Álvarez-Manzaneda E, Chahboun R, et al. Novel merosesquiterpene exerts a potent antitumor activity against breast cancer cells in vitro and in vivo. Eur J Med Chem. 2014;79:1–12.

    Article  CAS  PubMed  Google Scholar 

  40. Johnstone RM. Exosomes biological significance: a concise review. Blood Cells Mol Dis. 2006;36(2):315–21.

    Article  CAS  PubMed  Google Scholar 

  41. Smalheiser NR. Exosomal transfer of proteins and RNAs at synapses in the nervous system. Biol Direct. 2007;2:35.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Del Conde I, Shrimpton CN, Thiagarajan P, López JA. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood. 2005;106(5):1604–11.

    Article  PubMed  Google Scholar 

  43. Lee TH, D’Asti E, Magnus N, Al-Nedawi K, Meehan B, Rak J. Microvesicles as mediators of intercellular communication in cancer—the emerging science of cellular “debris.”. Semin Immunopathol. 2011;33(5):455–67.

    Article  PubMed  Google Scholar 

  44. Hemler ME. Tetraspanin proteins promote multiple cancer stages. Nat Rev Cancer. 2014;14(1):49–60.

    Article  CAS  PubMed  Google Scholar 

  45. Maecker HT, Todd SC, Levy S. The tetraspanin superfamily: molecular facilitators. FASEB J. 1997;11(6):428–42.

    CAS  PubMed  Google Scholar 

  46. Königsberg R, Obermayr E, Bises G, Pfeiler G, Gneist M, Wrba F, et al. Detection of EpCAM positive and negative circulating tumor cells in metastatic breast cancer patients. Acta Oncol. 2011;50(5):700–10.

    Article  PubMed  Google Scholar 

  47. Théry C, Amigorena S, Raposo G, Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol. 2006;Chapter 3:Unit 3.22.

  48. Muller L, Hong C-S, Stolz DB, Watkins SC, Whiteside TL. Isolation of biologically-active exosomes from human plasma. J Immunol Methods. 2014;411:55–65.

    Article  CAS  PubMed  Google Scholar 

  49. Hong CS, Muller L, Boyiadzis M, Whiteside TL. Isolation and characterization of CD34+ blast-derived exosomes in acute myeloid leukemia. PLoS One. 2014;9(8):e103310.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Ciravolo V, Huber V, Ghedini GC, Venturelli E, Bianchi F, Campiglio M, et al. Potential role of HER2-overexpressing exosomes in countering trastuzumab-based therapy. J Cell Physiol. 2012;227(2):658–67.

    Article  CAS  PubMed  Google Scholar 

  51. King HW, Michael MZ, Gleadle JM. Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer. 2012;12:421.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Camacho L, Guerrero P, Marchetti D. MicroRNA and protein profiling of brain metastasis competent cell-derived exosomes. PLoS ONE. 2013;8(9):e73790.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Chen W, Liu X, Lv M, Chen L, Zhao J, Zhong S, et al. Exosomes from drug-resistant breast cancer cells transmit chemoresistance by a horizontal transfer of microRNAs. PLoS One. 2014;9(4):e95240.

    Article  PubMed Central  PubMed  Google Scholar 

  54. Jia S, Zocco D, Samuels ML, Chou MF, Chammas R, Skog J, et al. Emerging technologies in extracellular vesicle-based molecular diagnostics. Expert Rev Mol Diagn. 2014;14(3):307–21.

    Article  CAS  PubMed  Google Scholar 

  55. Hu G, Drescher KM, Chen X. Exosomal miRNAs: biological properties and therapeutic potential. Front Genet. 2012;3:56.

    CAS  PubMed Central  PubMed  Google Scholar 

  56. Chen W-X, Cai Y-Q, Lv M-M, Chen L, Zhong S-L, Ma T-F, et al. Exosomes from docetaxel-resistant breast cancer cells alter chemosensitivity by delivering microRNAs. Tumour Biol. 2014;35(10):9649–59.

  57. Wei Y, Lai X, Yu S, Chen S, Ma Y, Zhang Y, et al. Exosomal miR-221/222 enhances tamoxifen resistance in recipient ER-positive breast cancer cells. Breast Cancer Res Treat. 2014;147(2):423–31.

    Article  CAS  PubMed  Google Scholar 

  58. van Balkom BWM, de Jong OG, Smits M, Brummelman J, den Ouden K, de Bree PM, et al. Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells. Blood. 2013;121(19):3997–4006.

    Article  PubMed  Google Scholar 

  59. Ohshima K, Inoue K, Fujiwara A, Hatakeyama K, Kanto K, Watanabe Y, et al. Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PLoS One. 2010;5(10):e13247.

    Article  PubMed Central  PubMed  Google Scholar 

  60. Dolo V, Adobati E, Canevari S, Picone MA, Vittorelli ML. Membrane vesicles shed into the extracellular medium by human breast carcinoma cells carry tumor-associated surface antigens. Clin Exp Metastasis. 1995;13(4):277–86.

    Article  CAS  PubMed  Google Scholar 

  61. Vizio DD, Kim J, Hager MH, Morello M, Yang W, Lafargue CJ, et al. Oncosome formation in prostate cancer: association with a region of frequent chromosomal deletion in metastatic disease. Cancer Res. 2009;69(13):5601–9.

    Article  PubMed Central  PubMed  Google Scholar 

  62. Somasundaram R, Herlyn M. Melanoma exosomes: messengers of metastasis. Nat Med. 2012;18(6):853–4.

    Article  CAS  PubMed  Google Scholar 

  63. DiMarino AM, Caplan AI, Bonfield TL. Mesenchymal stem cells in tissue repair. Inflammation. 2013;4:201.

    Google Scholar 

  64. Hung S-C, Deng W-P, Yang WK, Liu R-S, Lee C-C, Su T-C, et al. Mesenchymal stem cell targeting of microscopic tumors and tumor stroma development monitored by noninvasive in vivo positron emission tomography imaging. Clin Cancer Res. 2005;11(21):7749–56.

    Article  CAS  PubMed  Google Scholar 

  65. Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449(7162):557–63.

    Article  CAS  PubMed  Google Scholar 

  66. Krtolica A, Parrinello S, Lockett S, Desprez P-Y, Campisi J. Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc Natl Acad Sci. 2001;98(21):12072–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Xu D, Tahara H. The role of exosomes and microRNAs in senescence and aging. Adv Drug Deliv Rev. 2013;65(3):368–75.

    Article  CAS  PubMed  Google Scholar 

  68. Mitomo S, Maesawa C, Ogasawara S, Iwaya T, Shibazaki M, Yashima-Abo A, et al. Downregulation of miR-138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines. Cancer Sci. 2008;99(2):280–6.

    Article  CAS  PubMed  Google Scholar 

  69. Zhang Y, Yang P, Wang X-F. Microenvironmental regulation of cancer metastasis by miRNAs. Trends Cell Biol. 2014;24(3):153–60.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Campelo R, Lozano ID, Figarella K, Osuna A, Ramírez JL. Leishmania major telomerase TERT protein has a nuclear-mitochondrial-eclipsed distribution that is affected by oxidative stress. Infect Immun. 2014;83(1):57–66.

    Article  PubMed Central  PubMed  Google Scholar 

  71. Unsworth A, Anderson R, Britt K. Stromal fibroblasts and the immune microenvironment: partners in mammary gland biology and pathology? J Mammary Gland Biol Neoplasia. 2014;19(2):169–82.

    Article  PubMed  Google Scholar 

  72. Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer. 2009;9(4):239–52.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Goetz JG, Minguet S, Navarro-Lérida I, Lazcano JJ, Samaniego R, Calvo E, et al. Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell. 2011;146(1):148–63.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  74. Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R, et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell. 2005;121(3):335–48.

    Article  CAS  PubMed  Google Scholar 

  75. Erez N, Truitt M, Olson P, Arron ST, Hanahan D. Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner. Cancer Cell. 2010;17(2):135–47.

    Article  CAS  PubMed  Google Scholar 

  76. Thomas SN, Liao Z, Clark D, Chen Y, Samadani R, Mao L, et al. Exosomal proteome profiling: a potential multi-marker cellular phenotyping tool to characterize hypoxia-induced radiation resistance in breast cancer. Proteomes. 2013;1(2):87–108.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Jessen JR. Noncanonical Wnt signaling in tumor progression and metastasis. Zebrafish. 2009;6(1):21–8.

    Article  CAS  PubMed  Google Scholar 

  78. Khan S, Aspe JR, Asumen MG, Almaguel F, Odumosu O, Acevedo-Martinez S, et al. Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential. Br J Cancer. 2009;100(7):1073–86.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Pilzer D, Fishelson Z. Mortalin/GRP75 promotes release of membrane vesicles from immune attacked cells and protection from complement-mediated lysis. Int Immunol. 2005;17(9):1239–48.

    Article  CAS  PubMed  Google Scholar 

  80. Zhang H-G, Liu C, Su K, Su K, Yu S, Zhang L, et al. A membrane form of TNF-alpha presented by exosomes delays T cell activation-induced cell death. J Immunol. 2006;176(12):7385–93.

    Article  CAS  PubMed  Google Scholar 

  81. Hupfeld T, Chapuy B, Schrader V, Beutler M, Veltkamp C, Koch R, et al. Tyrosinekinase inhibition facilitates cooperation of transcription factor SALL4 and ABC transporter A3 towards intrinsic CML cell drug resistance. Br J Haematol. 2013;161(2):204–13.

    Article  CAS  PubMed  Google Scholar 

  82. Safaei R, Larson BJ, Cheng TC, Gibson MA, Otani S, Naerdemann W, et al. Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells. Mol Cancer Ther. 2005;4(10):1595–604.

    Article  CAS  PubMed  Google Scholar 

  83. Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP–dependent transporters. Nat Rev Cancer. 2002;2(1):48–58.

    Article  CAS  PubMed  Google Scholar 

  84. Azmi AS, Bao B, Sarkar FH. Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev. 2013;32(3–4):623–42.

    Article  CAS  PubMed  Google Scholar 

  85. Corcoran C, Rani S, O’Brien K, O’Neill A, Prencipe M, Sheikh R, et al. Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes. PLoS One. 2012;7(12):e50999.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  86. Shedden K, Xie XT, Chandaroy P, Chang YT, Rosania GR. Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles. Cancer Res. 2003;63(15):4331–7.

    CAS  PubMed  Google Scholar 

  87. Ifergan I, Scheffer GL, Assaraf YG. Novel extracellular vesicles mediate an ABCG2-dependent anticancer drug sequestration and resistance. Cancer Res. 2005;65(23):10952–8.

    Article  CAS  PubMed  Google Scholar 

  88. Goler-Baron V, Sladkevich I, Assaraf YG. Inhibition of the PI3K-Akt signaling pathway disrupts ABCG2-rich extracellular vesicles and overcomes multidrug resistance in breast cancer cells. Biochem Pharmacol. 2012;83(10):1340–8.

    Article  CAS  PubMed  Google Scholar 

  89. Tagliabue E, Balsari A, Campiglio M, Pupa SM. HER2 as a target for breast cancer therapy. Expert Opin Biol Ther. 2010;10(5):711–24.

    Article  CAS  PubMed  Google Scholar 

  90. Ng EKO, Tsui NBY, Lam NYL, Chiu RWK, Yu SCH, Wong SCC, et al. Presence of filterable and nonfilterable mRNA in the plasma of cancer patients and healthy individuals. Clin Chem. 2002;48(8):1212–7.

    CAS  PubMed  Google Scholar 

  91. Rabinowits G, Gerçel-Taylor C, Day JM, Taylor DD, Kloecker GH. Exosomal MicroRNA: a diagnostic marker for lung cancer. Clin Lung Cancer. 2009;10(1):42–6.

    Article  CAS  PubMed  Google Scholar 

  92. Zhang L, Xiao H, Karlan S, Zhou H, Gross J, Elashoff D, et al. Discovery and preclinical validation of salivary transcriptomic and proteomic biomarkers for the non-invasive detection of breast cancer. PLoS One. 2010;5(12):e15573.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  93. Caldas H, Jiang Y, Holloway MP, Fangusaro J, Mahotka C, Conway EM, et al. Survivin splice variants regulate the balance between proliferation and cell death. Oncogene. 2005;24(12):1994–2007.

    Article  CAS  PubMed  Google Scholar 

  94. Ryan B, O’Donovan N, Browne B, O’Shea C, Crown J, Hill ADK, et al. Expression of survivin and its splice variants survivin-2B and survivin-ΔEx3 in breast cancer. Br J Cancer. 2004;92(1):120–4.

    Article  PubMed Central  Google Scholar 

  95. Khan S, Bennit HF, Turay D, Perez M, Mirshahidi S, Yuan Y, et al. Early diagnostic value of survivin and its alternative splice variants in breast cancer. BMC Cancer. 2014;14:176.

    Article  PubMed Central  PubMed  Google Scholar 

  96. Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science. 2011;331(6024):1559–64.

    Article  CAS  PubMed  Google Scholar 

  97. Plaks V, Koopman CD, Werb Z. Circulating tumor cells. Science. 2013;341(6151):1186–8.

    Article  CAS  PubMed  Google Scholar 

  98. García-Olmo DC, García-Olmo D. Biological role of cell-free nucleic acids in cancer: the theory of genometastasis. Crit Rev Oncog. 2013;18(1–2):153–61.

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the Regional Government of Andalusia (Project P11-CTS-7651 and assistance to the CTS-107 and CTS-183 groups).

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Authors and Affiliations

  1. Institute of Biopathology and Regenerative Medicine, Biomedical Research Centre, University of Granada, 18016, Granada, Spain

    Alejandro Villagrasa, Pablo Juan Álvarez, Antonia Aránega & Fernando Rodríguez-Serrano

  2. Institute of Biotechnology, University of Granada, 18071, Granada, Spain

    Antonio Osuna

  3. Department of Cardiovascular Surgery, Virgen de las Nieves Hospital, 18014, Granada, Spain

    Jose Manuel Garrido

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  1. Alejandro Villagrasa
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  2. Pablo Juan Álvarez
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Correspondence to Fernando Rodríguez-Serrano.

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Villagrasa, A., Álvarez, P.J., Osuna, A. et al. Exosomes Derived from Breast Cancer Cells, Small Trojan Horses?. J Mammary Gland Biol Neoplasia 19, 303–313 (2014). https://doi.org/10.1007/s10911-015-9332-5

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