Skip to main content

Advertisement

SpringerLink
Log in

MicroRNAs delivered by extracellular vesicles: an emerging resistance mechanism for breast cancer

  • Review
  • Published:
Tumor Biology

Abstract

Resistance to chemotherapy and endocrine therapy as well as targeted drugs is a major problem in treatment of breast cancer. Over the last decades, emerging studies have revealed that extracellular vesicles, which are chronically released by breast cancer cells and surrounding stromal cells, influence the action of most commonly used therapeutics. Such modulatory effects have been related to the transport of biologically active molecules including proteins and functional microRNAs. In this review, we highlight recent studies regarding extracellular vesicle-mediated microRNA delivery in formatting drug resistance. We also suggest the use of extracellular vesicles as a promising method in antiresistance treatment.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

EV:

Extracellular vesicle

BCa:

Breast cancer

miRNA:

MicroRNA

mRNA:

Message RNA

P-gp:

P-glycoprotein

mdr 1:

Multidrug resistance 1

PDGF:

Platelet-derived growth factor

EGFR:

Epidermal growth factor receptor

ECs:

Endothelial cells

VEGF:

Vascular endothelial growth factor

TLR:

Toll-like receptor

TAMs:

Tumor-associated macrophages

DCs:

Dendritic cells

siRNA:

Small interfering RNA

EGF:

Epidermal growth factor

References

  1. Yuana Y, Sturk A, Nieuwland R. Extracellular vesicles in physiological and pathological conditions. Blood Rev. 2013;27(1):31–9.

    Article  PubMed  CAS  Google Scholar 

  2. Cocucci E, Racchetti G, Meldolesi J. Shedding microvesicles: artefacts no more. Trends Cell Biol. 2009;19(2):43–51.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  4. 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 

  5. Taylor DD, Gercel-Taylor C. Exosomes/microvesicles: mediators of cancer-associated immunosuppressive microenvironments. Semin Immunopathol. 2011;33(5):441–54.

    Article  PubMed  CAS  Google Scholar 

  6. Bussolati B, Grange C, Camussi G. Tumor exploits alternative strategies to achieve vascularization. FASEB J. 2011;25(9):2874–82.

    Article  PubMed  CAS  Google Scholar 

  7. Kahlert C, Kalluri R. Exosomes in tumor microenvironment influence cancer progression and metastasis. J Mol Med (Berl). 2013;91(4):431–7.

    Article  PubMed  CAS  Google Scholar 

  8. Peinado H, Alečković M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med. 2012;18(6):883–91.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  9. Gottesman MM. Mechanisms of cancer drug resistance. Annu Rev Med. 2002;53:615–27.

    Article  PubMed  CAS  Google Scholar 

  10. Goler-Baron V, Assaraf YG. Structure and function of ABCG2-rich extracellular vesicles mediating multidrug resistance. PLoS One. 2011;6(1):e16007.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  11. 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  PubMed  CAS  Google Scholar 

  12. Bebawy M, Combes V, Lee E, Jaiswal R, Gong J, Bonhoure A, et al. Membrane microparticles mediate transfer of P-glycoprotein to drug sensitive cancer cells. Leukemia. 2009;23(9):1643–9.

    Article  PubMed  CAS  Google Scholar 

  13. Pasquier J, Galas L, Boulangé-Lecomte C, Rioult D, Bultelle F, Magal P, et al. Different modalities of intercellular membrane exchanges mediate cell-to-cell p-glycoprotein transfers in MCF-7 breast cancer cells. J Biol Chem. 2012;287(10):7374–87.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  14. Chiba M, Kimura M, Asari S. Exosomes secreted from human colorectal cancer cell lines contain mRNAs, microRNAs and natural antisense RNAs, that can transfer into the human hepatoma HepG2 and lung cancer A549 cell lines. Oncol Rep. 2012;28(5):1551–8.

    PubMed Central  PubMed  CAS  Google Scholar 

  15. Gong J, Jaiswal R, Mathys JM, Combes V, Grau GE, Bebawy M. Microparticles and their emerging role in cancer multidrug resistance. Cancer Treat Rev. 2012;38(3):226–34.

    Article  PubMed  CAS  Google Scholar 

  16. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Kong YW, Ferland-McCollough D. Jackson TJ. Bushell M microRNAs in cancer managementLancet Oncol. 2012;13(6):e249–58.

    CAS  Google Scholar 

  18. Sarkar FH, Li Y, Wang Z, Kong D, Ali S. Implication of microRNAs in drug resistance for designing novel cancer therapy. Drug Resist Updat. 2010;13(3):57–66.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105(30):10513–8.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Park NJ, Zhou H, Elashoff D, Henson BS, Kastratovic DA, Abemayor E, et al. Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res. 2009;15(17):5473–7.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Hanke M, Hoefig K, Merz H, Feller AC, Kausch I, Jocham D, et al. A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. Urol Oncol. 2010;28(6):655–61.

    Article  PubMed  CAS  Google Scholar 

  22. Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, et al. Serum microRNAs are promising novel biomarkers. PLoS One. 2008;3(9):e3148.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Palma J, Yaddanapudi SC, Pigati L, Havens MA, Jeong S, Weiner GA, et al. MicroRNAs are exported from malignant cells in customized particles. Nucleic Acids Res. 2012;40(18):9125–38.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  24. Li L, Zhu D, Huang L, Zhang J, Bian Z, Chen X, et al. Argonaute 2 complexes selectively protect the circulating microRNAs in cell-secreted microvesicles. PLoS One. 2012;7(10):e46957.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R, Dvorak P, et al. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia. 2006;20(5):847–56.

    Article  PubMed  CAS  Google Scholar 

  26. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–9.

    Article  PubMed  CAS  Google Scholar 

  27. Hergenreider E, Heydt S, Tréguer K, Boettger T, Horrevoets AJ, Zeiher AM, et al. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol. 2012;14(3):249–56.

    Article  PubMed  CAS  Google Scholar 

  28. Morel L, Regan M, Higashimori H, Ng SK, Esau C, Vidensky S, et al. Neuronal exosomal miRNA-dependent translational regulation of astroglial glutamate transporter GLT1. J Biol Chem. 2013;288(10):7105–16.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  29. Keith WN, Stallard S, Brown R. Expression of mdr1 and gst-pi in human breast tumours: comparison to in vitro chemosensitivity. Br J Cancer. 1990;61(5):712–6.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  30. Kovalchuk O, Filkowski J, Meservy J, Ilnytskyy Y, Tryndyak VP, Chekhun VF, et al. Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Mol Cancer Ther. 2008;7(7):2152–9.

    Article  PubMed  CAS  Google Scholar 

  31. Pigati L, Yaddanapudi SC, Iyengar R, Kim DJ, Hearn SA, Danforth D, et al. Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS One. 2010;5(10):e13515.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  32. Goda K, Bacsó Z, Szabó G. Multidrug resistance through the spectacle of P-glycoprotein. Curr Cancer Drug Targets. 2009;9(3):281–97.

    Article  PubMed  CAS  Google Scholar 

  33. Bergamaschi A, Katzenellenbogen BS. Tamoxifen downregulation of miR-451 increases 14-3-3ζ and promotes breast cancer cell survival and endocrine resistance. Oncogene. 2012;31(1):39–47.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  34. Kastl L, Brown I, Schofield AC. miRNA-34a is associated with docetaxel resistance in human breast cancer cells. Breast Cancer Res Treat. 2012;131(2):445–54.

    Article  PubMed  CAS  Google Scholar 

  35. Jung EJ, Santarpia L, Kim J, Esteva FJ, Moretti E, Buzdar AU, et al. Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. Cancer. 2012;118(10):2603–14.

    Article  PubMed  CAS  Google Scholar 

  36. Wang J, Chen J, Chang P, LeBlanc A, Li D, Abbruzzesse JL, et al. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila). 2009;2(9):807–13.

    Article  PubMed  CAS  Google Scholar 

  37. Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, 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  PubMed Central  PubMed  CAS  Google Scholar 

  38. Mao Y, Keller ET, Garfield DH, Shen K, Wang J. Stromal cells in tumor microenvironment and breast cancer. Cancer Metastasis Rev. 2013;32(1–2):303–15.

    Article  PubMed  Google Scholar 

  39. Castells M, Thibault B, Delord JP, Couderc B. Implication of tumor microenvironment in chemoresistance: tumor-associated stromal cells protect tumor cells from cell death. Int J Mol Sci. 2012;13(8):9545–71.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  40. Hervé JC, Derangeon M. Gap-junction-mediated cell-to-cell communication. Cell Tissue Res. 2013;352(1):21–31.

    Article  PubMed  CAS  Google Scholar 

  41. Singer SJ. Intercellular communication and cell-cell adhesion. Science. 1992;255(5052):1671–7.

    Article  PubMed  CAS  Google Scholar 

  42. Imagawa W, Pedchenko VK, Helber J, Zhang H. Hormone/growth factor interactions mediating epithelial/stromal communication in mammary gland development and carcinogenesis. J Steroid Biochem Mol Biol. 2002;80(2):213–30.

    Article  PubMed  CAS  Google Scholar 

  43. Chen X, Liang H, Zhang J, Zen K, Zhang CY. Secreted microRNAs: a new form of intercellular communication. Trends Cell Biol. 2012;22(3):125–32.

    Article  PubMed  CAS  Google Scholar 

  44. Hannafon BN, Ding WQ. Intercellular communication by exosome-derived microRNAs in cancer. Int J Mol Sci. 2013;14(7):14240–69.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  45. Ng CK, Pemberton HN, Reis-Filho JS. Breast cancer intratumor genetic heterogeneity: causes and implications. Expert Rev Anticancer Ther. 2012;12(8):1021–32.

    Article  PubMed  CAS  Google Scholar 

  46. Levchenko A, Mehta BM, Niu X, Kang G, Villafania L, Way D, et al. Intercellular transfer of P-glycoprotein mediates acquired multidrug resistance in tumor cells. Proc Natl Acad Sci U S A. 2005;102(6):1933–8.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  47. Jaiswal R, Luk F, Dalla PV, Grau GE, Bebawy M. Breast cancer-derived microparticles display tissue selectivity in the transfer of resistance proteins to cells. PLoS One. 2013;8(4):e61515.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  48. Jaiswal R, Gong J, Sambasivam S, Combes V, Mathys JM, Davey R, et al. Microparticle-associated nucleic acids mediate trait dominance in cancer. FASEB J. 2012;26(1):420–9.

    Article  PubMed  CAS  Google Scholar 

  49. Jaiswal R, Luk F, Gong J, Mathys JM, Grau GE, Bebawy M. Microparticle conferred microRNA profiles–implications in the transfer and dominance of cancer traits. Mol Cancer. 2012;11:37.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  50. Kogure T, Lin WL, Yan IK, Braconi C, Patel T. Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth. Hepatology. 2011;54(4):1237–48.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  51. Gradilone A, Naso G, Raimondi C, Cortesi E, Gandini O, Vincenzi B, et al. Circulating tumor cells (CTCs) in metastatic breast cancer (MBC): prognosis, drug resistance and phenotypic characterization. Ann Oncol. 2011;22(1):86–92.

    Article  PubMed  CAS  Google Scholar 

  52. Korkaya H, Liu S, Wicha MS. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest. 2011;121(10):3804–9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  53. McMillin DW, Negri JM, Mitsiades CS. The role of tumour-stromal interactions in modifying drug response: challenges and opportunities. Nat Rev Drug Discov. 2013;12(3):217–28.

    Article  PubMed  CAS  Google Scholar 

  54. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  PubMed  CAS  Google Scholar 

  55. Kucharzewska P, Christianson HC, Welch JE, Svensson KJ, Fredlund E, Ringnér M, et al. 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;110(18):7312–7.

    Article  PubMed Central  PubMed  Google Scholar 

  56. Al-Nedawi K, Meehan B, Kerbel RS, Allison AC, Rak J. Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR. Proc Natl Acad Sci U S A. 2009;106(10):3794–9.

    Article  PubMed Central  PubMed  Google Scholar 

  57. Zhuang G, Wu X, Jiang Z, Kasman I, Yao J, Guan Y, et al. Tumour-secreted miR-9 promotes endothelial cell migration and angiogenesis by activating the JAK-STAT pathway. EMBO J. 2012;31(17):3513–23.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  58. Kosaka N, Iguchi H, Hagiwara K, Yoshioka Y, Takeshita F, Ochiya T. Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic microRNAs regulate cancer cell metastasis. J Biol Chem. 2013;288(15):10849–59.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  59. Grange C, Tapparo M, Collino F, Vitillo L, Damasco C, Deregibus MC, et al. Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche. Cancer Res. 2011;71(15):5346–56.

    Article  PubMed  CAS  Google Scholar 

  60. Bobrie A, Colombo M, Raposo G, Théry C. Exosome secretion: molecular mechanisms and roles in immune responses. Traffic. 2011;12(12):1659–68.

    Article  PubMed  CAS  Google Scholar 

  61. Abusamra AJ, Zhong Z, Zheng X, Li M, Ichim TE, Chin JL, et al. Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis. Blood Cells Mol Dis. 2005;35(2):169–73.

    Article  PubMed  CAS  Google Scholar 

  62. Valenti R, Huber V, Filipazzi P, Pilla L, Sovena G, Villa A, et al. Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-beta-mediated suppressive activity on T lymphocytes. Cancer Res. 2006;66(18):9290–8.

    Article  PubMed  CAS  Google Scholar 

  63. Szajnik M, Czystowska M, Szczepanski MJ, Mandapathil M, Whiteside TL. Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T cells (Treg). PLoS One. 2010;5(7):e11469.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  64. Ashiru O, Boutet P, Fernández-Messina L, Agüera-González S, Skepper JN, Valés-Gómez M, et al. Natural killer cell cytotoxicity is suppressed by exposure to the human NKG2D ligand MICA*008 that is shed by tumor cells in exosomes. Cancer Res. 2010;70(2):481–9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  65. Filipazzi P, Bürdek M, Villa A, Rivoltini L, Huber V. Recent advances on the role of tumor exosomes in immunosuppression and disease progression. Semin Cancer Biol. 2012;22(4):342–9.

    Article  PubMed  CAS  Google Scholar 

  66. Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci U S A. 2012;109(31):E2110–6.

    Article  PubMed Central  PubMed  Google Scholar 

  67. Hayes E, Nicholson RI, Hiscox S. Acquired endocrine resistance in breast cancer: implications for tumour metastasis. Front Biosci (Landmark Ed). 2011;16:838–48.

    Article  PubMed  CAS  Google Scholar 

  68. Baj-Krzyworzeka M, Szatanek R, Weglarczyk K, Baran J, Urbanowicz B, Brański P, et al. Tumour-derived microvesicles carry several surface determinants and mRNA of tumour cells and transfer some of these determinants to monocytes. Cancer Immunol Immunother. 2006;55(7):808–18.

    Article  PubMed  CAS  Google Scholar 

  69. Yang M, Chen J, Su F, Yu B, Su F, Lin L, et al. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells. Mol Cancer. 2011;10:117.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  70. 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  PubMed  CAS  Google Scholar 

  71. 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 U S A. 2011;108(12):4852–7.

    Article  PubMed Central  PubMed  Google Scholar 

  72. D'Souza-Schorey C, Clancy JW. Tumor-derived microvesicles: shedding light on novel microenvironment modulators and prospective cancer biomarkers. Genes Dev. 2012;26(12):1287–99.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  73. Mansfield AS, Heikkila P, von Smitten K, Vakkila J, Leidenius M. Metastasis to sentinel lymph nodes in breast cancer is associated with maturation arrest of dendritic cells and poor co-localization of dendritic cells and CD8+ T cells. Virchows Arch. 2011;459(4):391–8.

    Article  PubMed  CAS  Google Scholar 

  74. Montecalvo A, Larregina AT, Shufesky WJ, Stolz DB, Sullivan ML, Karlsson JM, et al. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood. 2012;119(3):756–66.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  75. Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, et al. Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci U S A. 2010;107(14):6328–33.

    Article  PubMed Central  PubMed  Google Scholar 

  76. Lazzeri E, Romagnani P. CXCR3-binding chemokines: novel multifunctional therapeutic targets. Curr Drug Targets Immune Endocr Metabol Disord. 2005;5(1):109–18.

    Article  PubMed  CAS  Google Scholar 

  77. Mittelbrunn M, Gutiérrez-Vázquez C, Villarroya-Beltri C, González S, Sánchez-Cabo F, González M, et al. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun. 2011;2:282.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  78. Ismail N, Wang Y, Dakhlallah D, Moldovan L, Agarwal K, Batte K, et al. Macrophage microvesicles induce macrophage differentiation and miR-223 transfer. Blood. 2013;121(6):984–95.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  79. Cekaite L, Clancy T, Sioud M. Increased miR-21 expression during human monocyte differentiation into DCs. Front Biosci (Elite Ed). 2010;2:818–28.

    Article  PubMed  Google Scholar 

  80. Zhang Y, Liu D, Chen X, Li J, Li L, Bian Z, et al. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol Cell. 2010;39(1):133–44.

    Article  PubMed  CAS  Google Scholar 

  81. Baer C, Squadrito ML, Iruela-Arispe ML, De Palma M. Reciprocal interactions between endothelial cells and macrophages in angiogenic vascular niches. Exp Cell Res. 2013. doi:10.1016/j.yexcr.2013.03.026.

    PubMed  Google Scholar 

  82. Collino F, Deregibus MC, Bruno S, Sterpone L, Aghemo G, Viltono L, et al. Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS One. 2010;5(7):e11803.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  83. Ogawa R, Tanaka C, Sato M, Nagasaki H, Sugimura K, Okumura K, et al. Adipocyte-derived microvesicles contain RNA that is transported into macrophages and might be secreted into blood circulation. Biochem Biophys Res Commun. 2010;398(4):723–9.

    Article  PubMed  CAS  Google Scholar 

  84. Jain RK. Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. J Clin Oncol. 2013;31(17):2205–18.

    Article  PubMed  CAS  Google Scholar 

  85. van den Boorn JG, Schlee M, Coch C, Hartmann G. SiRNA delivery with exosome nanoparticles. Nat Biotechnol. 2011;29(4):325–6.

    Article  PubMed  CAS  Google Scholar 

  86. Kooijmans SA, Vader P, van Dommelen SM, van Solinge WW, Schiffelers RM. Exosome mimetics: a novel class of drug delivery systems. Int J Nanomedicine. 2012;7:1525–41.

    PubMed Central  PubMed  CAS  Google Scholar 

  87. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29(4):341–5.

    Article  PubMed  CAS  Google Scholar 

  88. Mizrak A, Bolukbasi MF, Ozdener GB, Brenner GJ, Madlener S, Erkan EP, et al. Genetically engineered microvesicles carrying suicide mRNA/protein inhibit schwannoma tumor growth. Mol Ther. 2013;21(1):101–8.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  89. Ohno S, Takanashi M, Sudo K, Ueda S, Ishikawa A, Matsuyama N, et al. Mol Ther. 2013;21(1):185–91.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  90. O'Day E, Lal A. MicroRNAs and their target gene networks in breast cancer. Breast Cancer Res. 2010;12(2):201.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  91. Lu Y, Roy S, Nuovo G, Ramaswamy B, Miller T, Shapiro C, et al. Anti-microRNA-222 (anti-miR-222) and -181B suppress growth of tamoxifen-resistant xenografts in mouse by targeting TIMP3 protein and modulating mitogenic signal. J Biol Chem. 2011;286(49):42292–302.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to acknowledge the funding body for supporting this work: the National Natural Science Foundation of China provided to Jin-hai Tang and Jian-hua Zhao. We also thank Jian-Zhong Wu for his discussions and help in our manuscript.

Conflicts of interest

None

Author information

Authors and Affiliations

  1. The Fourth Clinical School of Nanjing Medical University, Nanjing, 210029, China

    Wei-xian Chen, Meng Pan, Meng-meng Lv & Zhou Luo

  2. Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Baiziting, Nanjing, 210009, China

    Wei-xian Chen, Ming-hua Ji, Qing Hu, Meng-meng Lv, Zhou Luo & Jin-hai Tang

  3. Center of Clinical Laboratory, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Baiziting, Nanjing, 210009, China

    Shan-liang Zhong & Jian-hua Zhao

  4. Graduate School, Xuzhou Medical College, Xuzhou, 221002, China

    Qing Hu

Authors
  1. Wei-xian Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shan-liang Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ming-hua Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Meng Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qing Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Meng-meng Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhou Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jian-hua Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jin-hai Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jian-hua Zhao or Jin-hai Tang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, Wx., Zhong, Sl., Ji, Mh. et al. MicroRNAs delivered by extracellular vesicles: an emerging resistance mechanism for breast cancer. Tumor Biol. 35, 2883–2892 (2014). https://doi.org/10.1007/s13277-013-1417-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-013-1417-4

Keywords

Search

Navigation