Skip to main content

Advertisement

SpringerLink
Log in

Recent Advances in Experimental Models of Breast Cancer Exosome Secretion, Characterization and Function

  • Published:
Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Breast cancer (BC) is responsible for 15% of all the cancer deaths among women in the USA. The tumor microenvironment (TME) has the potential to act as a driver of breast cancer progression and metastasis. The TME is composed of stromal cells within an extracellular matrix and soluble cytokines, chemokines and extracellular vesicles and nanoparticles that actively influence cell behavior. Extracellular vesicles include exosomes, microvesicles and large oncosomes that orchestrate fundamental processes during tumor progression through direct interaction with target cells. Long before tumor cell spread to future metastatic sites, tumor-secreted exosomes enter the circulation and establish distant pre-metastatic niches, hospitable and permissive milieus for metastatic colonization. Emerging evidence suggests that breast cancer exosomes promote tumor progression and metastasis by inducing vascular leakiness, angiogenesis, invasion, immunomodulation and chemoresistance. Exosomes are found in almost all physiological fluids including plasma, urine, saliva, and breast milk, providing a valuable resource for the development of non-invasive cancer biomarkers. Here, we review work on the role of exosomes in breast cancer progression and metastasis, and describe the most recent advances in models of exosome secretion, isolation, characterization and functional analysis. We highlight the potential applications of plasma-derived exosomes as predictive biomarkers for breast cancer diagnosis, prognosis and therapy monitoring. We finally describe the therapeutic approaches of exosomes in breast cancer.

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

AF4:

Asymmetric flow field-flow fractionation

AFM:

Atomic force microscopy

BC:

Breast cancer

DC:

Dendritic cell

DCIS:

Ductal carcinoma in situ

ELISA:

Enzyme-linked immunosorbent assay

EV:

Extracellular vesicle

HMEC:

Human mammary epithelial cells

K:

Cytokeratin

MS:

Mass spectrometry

MV:

Microvesicle

NACT:

Neoadjuvant chemotherapy

NK:

Natural killer

NTA:

Nanoparticle tracking analysis

PMN:

Pre-metastatic niche

TDLU:

Terminal ductal lobular unit

TEM:

Transmission electron microscopy

TME:

Tumor microenvironment

WB:

Western blot

References

  1. Feng Y, et al. Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes Dis. 2018;5(2):77–106.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Radisky DC, et al. Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature. 2005;436(7047):123–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Gudjonsson T, et al. Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition. J Cell Sci. 2002;115(Pt 1):39–50.

    CAS  PubMed  Google Scholar 

  4. Bhowmick NA, et al. TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science. 2004;303(5659):848–51.

    CAS  PubMed  Google Scholar 

  5. Finak G, et al. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med. 2008;14(5):518–27.

    CAS  PubMed  Google Scholar 

  6. Ingthorsson S, et al. Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3D culture. BMC Res Notes. 2010;3:184.

    PubMed  PubMed Central  Google Scholar 

  7. Kraman M, et al. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science. 2010;330(6005):827–30.

    CAS  PubMed  Google Scholar 

  8. Psaila B, Lyden D. The metastatic niche: adapting the foreign soil. Nat Rev Cancer. 2009;9(4):285–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Hoshino A, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527(7578):329–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Wortzel I, et al. Exosome-Mediated Metastasis: Communication from a Distance. Dev Cell. 2019;49(3):347–60.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  12. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science, 2020. 367(6478).

  13. Mathieu M, et al. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019;21(1):9–17.

    CAS  PubMed  Google Scholar 

  14. Skotland T, et al. An emerging focus on lipids in extracellular vesicles. Adv Drug Deliv Rev, 2020.

  15. van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213–28.

    PubMed  Google Scholar 

  16. Zhang H, et al. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat Cell Biol. 2018;20(3):332–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Fitzgerald W, et al. A System of Cytokines Encapsulated in ExtraCellular Vesicles. Sci Rep. 2018;8(1):8973.

    PubMed  PubMed Central  Google Scholar 

  18. Jeppesen DK, et al. Reassessment of exosome composition. Cell, 2019. 177(2): p. 428–445 e18.

  19. Ratajczak J, 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.

    CAS  PubMed  Google Scholar 

  20. Thakur BK, et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res. 2014;24(6):766–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Sansone P, et al. Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer. Proc Natl Acad Sci U S A. 2017;114(43):E9066–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Konoshenko MY, et al. Isolation of Extracellular Vesicles: General Methodologies and Latest Trends. Biomed Res Int. 2018;2018:8545347.

    PubMed  PubMed Central  Google Scholar 

  23. Peinado H, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med. 2012;18(6):883–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Witwer KW, et al. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles. 2013;2:20360.

    Google Scholar 

  25. Linares R, et al. High-speed centrifugation induces aggregation of extracellular vesicles. J Extracell Vesicles. 2015;4:29509.

    PubMed  Google Scholar 

  26. Sodar BW, et al. Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection. Sci Rep. 2016;6:24316.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Gupta S, et al. An improvised one-step sucrose cushion ultracentrifugation method for exosome isolation from culture supernatants of mesenchymal stem cells. Stem Cell Res Ther. 2018;9(1):180.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhang Q, et al. Transfer of functional cargo in exomeres. Cell Rep, 2019. 27(3): p. 940–954 e6.

  29. van der Pol E, et al. Optical and non-optical methods for detection and characterization of microparticles and exosomes. J Thromb Haemost. 2010;8(12):2596–607.

    PubMed  Google Scholar 

  30. Raposo G, et al. B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996;183(3):1161–72.

    CAS  PubMed  Google Scholar 

  31. Arraud N, et al. Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and concentration. J Thromb Haemost. 2014;12(5):614–27.

    CAS  PubMed  Google Scholar 

  32. Skliar M, Chernyshev VS. Imaging of extracellular vesicles by atomic force microscopy. J Vis Exp, 2019(151).

  33. Dragovic RA, et al. Sizing and phenotyping of cellular vesicles using Nanoparticle Tracking Analysis. Nanomedicine. 2011;7(6):780–8.

    CAS  PubMed  Google Scholar 

  34. Anderson W, et al. Observations of Tunable Resistive Pulse Sensing for Exosome Analysis: Improving System Sensitivity and Stability. Langmuir. 2015;31(23):6577–87.

    CAS  PubMed  Google Scholar 

  35. Kesimer M, Gupta R. Physical characterization and profiling of airway epithelial derived exosomes using light scattering. Methods. 2015;87:59–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Zheng Y, et al. Monitoring the Rab27 associated exosome pathway using nanoparticle tracking analysis. Exp Cell Res. 2013;319(12):1706–13.

    CAS  PubMed  Google Scholar 

  37. Soo CY, et al. Nanoparticle tracking analysis monitors microvesicle and exosome secretion from immune cells. Immunology. 2012;136(2):192–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Costa-Silva B, et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol. 2015;17(6):816–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Chiang CY, Chen C. Toward characterizing extracellular vesicles at a single-particle level. J Biomed Sci. 2019;26(1):9.

    PubMed  PubMed Central  Google Scholar 

  40. Steen HB. Flow cytometer for measurement of the light scattering of viral and other submicroscopic particles. Cytometry A. 2004;57(2):94–9.

    PubMed  Google Scholar 

  41. Hercher M, Mueller W, Shapiro HM. Detection and discrimination of individual viruses by flow cytometry. J Histochem Cytochem. 1979;27(1):350–2.

    CAS  PubMed  Google Scholar 

  42. Yang L, et al. Development of an ultrasensitive dual-channel flow cytometer for the individual analysis of nanosized particles and biomolecules. Anal Chem. 2009;81(7):2555–63.

    CAS  PubMed  Google Scholar 

  43. Lacroix R, et al. Overcoming limitations of microparticle measurement by flow cytometry. Semin Thromb Hemost. 2010;36(8):807–18.

    PubMed  Google Scholar 

  44. van der Vlist EJ, et al. Fluorescent labeling of nano-sized vesicles released by cells and subsequent quantitative and qualitative analysis by high-resolution flow cytometry. Nat Protoc. 2012;7(7):1311–26.

    PubMed  Google Scholar 

  45. Pospichalova V, et al. Simplified protocol for flow cytometry analysis of fluorescently labeled exosomes and microvesicles using dedicated flow cytometer. J Extracell Vesicles. 2015;4:25530.

    PubMed  Google Scholar 

  46. Morales-Kastresana A, et al. Labeling Extracellular Vesicles for Nanoscale Flow Cytometry. Sci Rep. 2017;7(1):1878.

    PubMed  PubMed Central  Google Scholar 

  47. van der Pol E, et al. Absolute sizing and label-free identification of extracellular vesicles by flow cytometry. Nanomedicine. 2018;14(3):801–10.

    PubMed  Google Scholar 

  48. Tamkovich SN, et al. Isolation and characterization of exosomes from blood plasma of breast cancer and colorectal cancer patients. Biomed Khim. 2017;63(2):165–9.

    CAS  PubMed  Google Scholar 

  49. Choi DS, et al. Proteomics of extracellular vesicles: Exosomes and ectosomes. Mass Spectrom Rev. 2015;34(4):474–90.

    CAS  PubMed  Google Scholar 

  50. Rontogianni S, et al. Proteomic profiling of extracellular vesicles allows for human breast cancer subtyping. Commun Biol. 2019;2:325.

    PubMed  PubMed Central  Google Scholar 

  51. Kahlert C, et al. 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. 2014;289(7):3869–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Pegtel DM, et al. Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci USA. 2010;107(14):6328–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Kosaka N, et al. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem. 2010;285(23):17442–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Zhang Y, et al. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol Cell. 2010;39(1):133–44.

    CAS  PubMed  Google Scholar 

  55. Prendergast EN, et al. Optimizing exosomal RNA isolation for RNA-Seq analyses of archival sera specimens. PLoS ONE. 2018;13(5):e0196913.

    PubMed  PubMed Central  Google Scholar 

  56. Tang YT, et al. Comparison of isolation methods of exosomes and exosomal RNA from cell culture medium and serum. Int J Mol Med. 2017;40(3):834–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Johnsen KB, et al. What is the blood concentration of extracellular vesicles? Implications for the use of extracellular vesicles as blood-borne biomarkers of cancer. Biochim Biophys Acta Rev Cancer. 2019;1871(1):109–16.

    CAS  PubMed  Google Scholar 

  58. Ando W, et al. Novel breast cancer screening: combined expression of miR-21 and MMP-1 in urinary exosomes detects 95% of breast cancer without metastasis. Sci Rep. 2019;9(1):13595.

    PubMed  PubMed Central  Google Scholar 

  59. Street JM, et al. Urine Exosome Isolation and Characterization. Methods Mol Biol. 2017;1641:413–23.

    CAS  PubMed  Google Scholar 

  60. Gheinani AH, et al. Improved isolation strategies to increase the yield and purity of human urinary exosomes for biomarker discovery. Sci Rep. 2018;8(1):3945.

    PubMed  PubMed Central  Google Scholar 

  61. Kang Y, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell. 2003;3(6):537–49.

    CAS  PubMed  Google Scholar 

  62. Gupta GP, et al. Identifying site-specific metastasis genes and functions. Cold Spring Harb Symp Quant Biol. 2005;70:149–58.

    CAS  PubMed  Google Scholar 

  63. Minn AJ, et al. Genes that mediate breast cancer metastasis to lung. Nature. 2005;436(7050):518–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Bos PD, et al. Genes that mediate breast cancer metastasis to the brain. Nature. 2009;459(7249):1005–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Li J, et al. Serum-free culture alters the quantity and protein composition of neuroblastoma-derived extracellular vesicles. J Extracell Vesicles. 2015;4:26883.

    PubMed  Google Scholar 

  66. Labarge MA, Garbe JC, Stampfer MR. Processing of human reduction mammoplasty and mastectomy tissues for cell culture. J Vis Exp. 2013;71:e50011.

    Google Scholar 

  67. Briem E, et al. Application of the D492 Cell Lines to Explore Breast Morphogenesis, EMT and Cancer Progression in 3D Culture. J Mammary Gland Biol Neoplasia. 2019;24(2):139–47.

    PubMed  Google Scholar 

  68. Garbe JC, et al. Molecular distinctions between stasis and telomere attrition senescence barriers shown by long-term culture of normal human mammary epithelial cells. Cancer Res. 2009;69(19):7557–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Lee JK, et al. Different culture media modulate growth, heterogeneity, and senescence in human mammary epithelial cell cultures. PLoS ONE. 2018;13(10):e0204645.

    PubMed  PubMed Central  Google Scholar 

  70. Garbe JC, et al. Immortalization of normal human mammary epithelial cells in two steps by direct targeting of senescence barriers does not require gross genomic alterations. Cell Cycle. 2014;13(21):3423–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Chanson L, et al. Self-organization is a dynamic and lineage-intrinsic property of mammary epithelial cells. Proc Natl Acad Sci USA. 2011;108(8):3264–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. LaBarge MA, et al. Breast Cancer beyond the Age of Mutation. Gerontology. 2016;62(4):434–42.

    CAS  PubMed  Google Scholar 

  73. Lin CH, et al. Microenvironment rigidity modulates responses to the HER2 receptor tyrosine kinase inhibitor lapatinib via YAP and TAZ transcription factors. Mol Biol Cell. 2015;26(22):3946–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Pelissier Vatter FA, et al. High-Dimensional Phenotyping Identifies Age-Emergent Cells in Human Mammary Epithelia. Cell Rep. 2018;23(4):1205–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Pelissier FA, et al. Age-related dysfunction in mechanotransduction impairs differentiation of human mammary epithelial progenitors. Cell Rep. 2014;7(6):1926–39.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Garbe JC, et al. Accumulation of multipotent progenitors with a basal differentiation bias during aging of human mammary epithelia. Cancer Res. 2012;72(14):3687–701.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Chin AR, et al. Polarized Secretion of Extracellular Vesicles by Mammary Epithelia. J Mammary Gland Biol Neoplasia. 2018;23(3):165–76.

    PubMed  PubMed Central  Google Scholar 

  78. Dutta S, et al. Interactions between exosomes from breast cancer cells and primary mammary epithelial cells leads to generation of reactive oxygen species which induce DNA damage response, stabilization of p53 and autophagy in epithelial cells. PLoS ONE. 2014;9(5):e97580.

    PubMed  PubMed Central  Google Scholar 

  79. Riches A, et al. Regulation of exosome release from mammary epithelial and breast cancer cells - a new regulatory pathway. Eur J Cancer. 2014;50(5):1025–34.

    CAS  PubMed  Google Scholar 

  80. Gonzalez E, et al. Human mammospheres secrete hormone-regulated active extracellular vesicles. PLoS ONE. 2014;9(1):e83955.

    PubMed  PubMed Central  Google Scholar 

  81. Rosenbluth JM, et al. Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages. Nat Commun. 2020;11(1):1711.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Admyre C, et al. Exosomes with immune modulatory features are present in human breast milk. J Immunol. 2007;179(3):1969–78.

    CAS  PubMed  Google Scholar 

  83. Pisano C, et al. Human Breast Milk-Derived Extracellular Vesicles in the Protection Against Experimental Necrotizing Enterocolitis. J Pediatr Surg. 2020;55(1):54–8.

    PubMed  Google Scholar 

  84. Liao Y, et al. Human milk exosomes and their microRNAs survive digestion in vitro and are taken up by human intestinal cells. Mol Nutr Food Res. 2017;61(11):1700082.

    Google Scholar 

  85. Yang Y, et al. Immunocompetent mouse allograft models for development of therapies to target breast cancer metastasis. Oncotarget. 2017;8(19):30621–43.

    PubMed  PubMed Central  Google Scholar 

  86. Fantozzi A, Christofori G. Mouse models of breast cancer metastasis. Breast Cancer Res. 2006;8(4):212.

    PubMed  PubMed Central  Google Scholar 

  87. Tsai PP, et al. Effects of different blood collection methods on indicators of welfare in mice. Lab Anim (NY). 2015;44(8):301–10.

    Google Scholar 

  88. Thompson C, Keck K, and Hielscher A. Isolation of Intact, Whole Mouse Mammary Glands for Analysis of Extracellular Matrix Expression and Gland Morphology. J Vis Exp. 2017(128).

  89. Smalley MJ. Isolation, culture and analysis of mouse mammary epithelial cells. Methods Mol Biol. 2010;633:139–70.

    CAS  PubMed  Google Scholar 

  90. Deugnier MA, et al. Isolation of mouse mammary epithelial progenitor cells with basal characteristics from the Comma-Dbeta cell line. Dev Biol. 2006;293(2):414–25.

    CAS  PubMed  Google Scholar 

  91. DePeters EJ, Hovey RC. Methods for collecting milk from mice. J Mammary Gland Biol Neoplasia. 2009;14(4):397–400.

    PubMed  PubMed Central  Google Scholar 

  92. Yu H, Mouw JK, Weaver VM. Forcing form and function: biomechanical regulation of tumor evolution. Trends Cell Biol. 2011;21(1):47–56.

    PubMed  Google Scholar 

  93. Northey JJ, Przybyla L, Weaver VM. Tissue Force Programs Cell Fate and Tumor Aggression. Cancer Discov. 2017;7(11):1224–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Bissell MJ, et al. The organizing principle: microenvironmental influences in the normal and malignant breast. Differentiation. 2002;70(9–10):537–46.

    PubMed  PubMed Central  Google Scholar 

  95. Lee GY, et al. Three-dimensional culture models of normal and malignant breast epithelial cells. Nat Methods. 2007;4(4):359–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Suetsugu A, et al. Imaging exosome transfer from breast cancer cells to stroma at metastatic sites in orthotopic nude-mouse models. Adv Drug Deliv Rev. 2013;65(3):383–90.

    CAS  PubMed  Google Scholar 

  97. Koumangoye RB, et al. Detachment of breast tumor cells induces rapid secretion of exosomes which subsequently mediate cellular adhesion and spreading. PLoS ONE. 2011;6(9):e24234.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Rodrigues G, et al. Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis. Nat Cell Biol. 2019;21(11):1403–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Wiklander OP, et al. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J Extracell Vesicles. 2015;4:26316.

    PubMed  Google Scholar 

  100. Rivoltini L, et al. TNF-Related Apoptosis-Inducing Ligand (TRAIL)-Armed Exosomes Deliver Proapoptotic Signals to Tumor Site. Clin Cancer Res. 2016;22(14):3499–512.

    CAS  PubMed  Google Scholar 

  101. Zhu L, et al. Novel alternatives to extracellular vesicle-based immunotherapy - exosome mimetics derived from natural killer cells. Artif Cells Nanomed Biotechnol. 2018;46(sup3):S166–79.

    CAS  PubMed  Google Scholar 

  102. Wen SW, et al. The Biodistribution and Immune Suppressive Effects of Breast Cancer-Derived Exosomes. Cancer Res. 2016;76(23):6816–27.

    CAS  PubMed  Google Scholar 

  103. Rashid MH, et al. Differential in vivo biodistribution of (131)I-labeled exosomes from diverse cellular origins and its implication for theranostic application. Nanomedicine. 2019;21:102072.

    CAS  PubMed  Google Scholar 

  104. O’Brien K, 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.

    CAS  PubMed  Google Scholar 

  105. Cho JA, et al. 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 

  106. Galindo-Hernandez O, et al. Extracellular vesicles from women with breast cancer promote an epithelial-mesenchymal transition-like process in mammary epithelial cells MCF10A. Tumour Biol. 2015;36(12):9649–59.

    CAS  PubMed  Google Scholar 

  107. Melo SA, et al. Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell. 2014;26(5):707–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Le MT, et al. miR-200-containing extracellular vesicles promote breast cancer cell metastasis. J Clin Invest. 2014;124(12):5109–28.

    PubMed  PubMed Central  Google Scholar 

  109. Antonyak MA, 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Zhou W, et al. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell. 2014;25(4):501–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Maji S, et al. Exosomal Annexin II Promotes Angiogenesis and Breast Cancer Metastasis. Mol Cancer Res. 2017;15(1):93–105.

    CAS  PubMed  Google Scholar 

  112. Othman N, Jamal R, Abu N. Cancer-Derived Exosomes as Effectors of Key Inflammation-Related Players. Front Immunol. 2019;10:2103.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Clayton A, Tabi Z. Exosomes and the MICA-NKG2D system in cancer. Blood Cells Mol Dis. 2005;34(3):206–13.

    CAS  PubMed  Google Scholar 

  114. Yu S, et al. Tumor exosomes inhibit differentiation of bone marrow dendritic cells. J Immunol. 2007;178(11):6867–75.

    CAS  PubMed  Google Scholar 

  115. Liu C, et al. Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. J Immunol. 2006;176(3):1375–85.

    CAS  PubMed  Google Scholar 

  116. Chow A, et al. Macrophage immunomodulation by breast cancer-derived exosomes requires Toll-like receptor 2-mediated activation of NF-kappaB. Sci Rep. 2014;4:5750.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. de Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 2006;6(1):24–37.

    PubMed  Google Scholar 

  118. Yang M, et al. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells. Mol Cancer. 2011;10:117.

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Rupp AK, et al. Loss of EpCAM expression in breast cancer derived serum exosomes: role of proteolytic cleavage. Gynecol Oncol. 2011;122(2):437–46.

    CAS  PubMed  Google Scholar 

  120. Khan S, et al. Early diagnostic value of survivin and its alternative splice variants in breast cancer. BMC Cancer. 2014;14:176.

    PubMed  PubMed Central  Google Scholar 

  121. Galindo-Hernandez O, et al. Elevated concentration of microvesicles isolated from peripheral blood in breast cancer patients. Arch Med Res. 2013;44(3):208–14.

    CAS  PubMed  Google Scholar 

  122. Kibria G, et al. A rapid, automated surface protein profiling of single circulating exosomes in human blood. Sci Rep. 2016;6:36502.

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Chen IH, et al. Phosphoproteins in extracellular vesicles as candidate markers for breast cancer. Proc Natl Acad Sci U S A. 2017;114(12):3175–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Hoshino A, et al. Extracellular vesicle and particle biomarkers define multiple human cancers.Cell, 2020;182(4): p. 1044–1061 e18.

  125. Konig L, et al. Elevated levels of extracellular vesicles are associated with therapy failure and disease progression in breast cancer patients undergoing neoadjuvant chemotherapy. Oncoimmunology. 2017;7(1):e1376153.

    PubMed  PubMed Central  Google Scholar 

  126. Keklikoglou I, et al. Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models. Nat Cell Biol. 2019;21(2):190–202.

    CAS  PubMed  Google Scholar 

  127. Chen Y, et al. Breast cancer resistance protein (BCRP)-containing circulating microvesicles contribute to chemoresistance in breast cancer. Oncol Lett. 2015;10(6):3742–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Thind A, Wilson C. Exosomal miRNAs as cancer biomarkers and therapeutic targets. J Extracell Vesicles. 2016;5:31292.

    PubMed  Google Scholar 

  129. Vigorito E, et al. miR-155: an ancient regulator of the immune system. Immunol Rev. 2013;253(1):146–57.

    PubMed  Google Scholar 

  130. Wei Y, et al. The microRNA-342-5p fosters inflammatory macrophage activation through an Akt1- and microRNA-155-dependent pathway during atherosclerosis. Circulation. 2013;127(15):1609–19.

    CAS  PubMed  Google Scholar 

  131. Delcayre A, et al. Exosome Display technology: applications to the development of new diagnostics and therapeutics. Blood Cells Mol Dis. 2005;35(2):158–68.

    CAS  PubMed  Google Scholar 

  132. Tian Y, et al. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials. 2014;35(7):2383–90.

    CAS  PubMed  Google Scholar 

  133. Wang L, et al. Exosomal pMHC-I complex targets T cell-based vaccine to directly stimulate CTL responses leading to antitumor immunity in transgenic FVBneuN and HLA-A2/HER2 mice and eradicating trastuzumab-resistant tumor in athymic nude mice. Breast Cancer Res Treat. 2013;140(2):273–84.

    CAS  PubMed  Google Scholar 

  134. Escudier B, et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial. J Transl Med. 2005;3(1):10.

    PubMed  PubMed Central  Google Scholar 

  135. Morse MA, et al. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J Transl Med. 2005;3(1):9.

    PubMed  PubMed Central  Google Scholar 

  136. Besse B, et al. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. Oncoimmunology. 2016;5(4):e1071008.

    PubMed  Google Scholar 

  137. Chen YS, et al. Exosomes in clinical trial and their production in compliance with good manufacturing practice. Ci Ji Yi Xue Za Zhi. 2019;32(2):113–20.

    PubMed  Google Scholar 

  138. Wong NC, et al. Alphav integrins mediate adhesion and migration of breast carcinoma cell lines. Clin Exp Metastasis. 1998;16(1):50–61.

    CAS  PubMed  Google Scholar 

  139. Jang JY, et al. Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumor-associated macrophage infiltration and M2 polarization. BMC Cancer. 2013;13:421.

    PubMed  PubMed Central  Google Scholar 

  140. Ohno S, et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther. 2013;21(1):185–91.

    CAS  PubMed  Google Scholar 

  141. Thery C, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge support from Dr. David Lyden.

The figures were created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com. F.A.V was supported by a Swiss National Science Foundation (SFNS) Postdoc.Mobility grant (P2SKP3_174785 and P400PB_186791). S.L was supported by United States Department of Defense W81XWH2010263-01. H.Z was supported by National Cancer Institute CA218513 and U19 AI144301-01.

Author information

Authors and Affiliations

  1. Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, NY, USA

    Fanny A. Pelissier Vatter, Serena Lucotti & Haiying Zhang

Authors
  1. Fanny A. Pelissier Vatter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Serena Lucotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haiying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The first draft of the manuscript was written by Fanny A. Pelissier Vatter who performed the literature search and data analysis. Serena Lucotti and Haiying Zhang critically revised the work.

Corresponding author

Correspondence to Fanny A. Pelissier Vatter.

Ethics declarations

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pelissier Vatter, F.A., Lucotti, S. & Zhang, H. Recent Advances in Experimental Models of Breast Cancer Exosome Secretion, Characterization and Function. J Mammary Gland Biol Neoplasia 25, 305–317 (2020). https://doi.org/10.1007/s10911-020-09473-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10911-020-09473-0

Keywords

Search

Navigation