Breast Cancer-Derived Extracellular Vesicles: Characterization and Contribution to the Metastatic Phenotype

The study of extracellular vesicles (EVs) in cancer progression is a complex and rapidly evolving field. Whole categories of cellular interactions in cancer which were originally presumed to be due solely to soluble secreted molecules have now evolved to include membrane-enclosed extracellular vesicles (EVs), which include both exosomes and shed microvesicles (MVs), and can contain many of the same molecules as those secreted in soluble form but many different molecules as well. EVs released by cancer cells can transfer mRNA, miRNA, and proteins to different recipient cells within the tumor microenvironment, in both an autocrine and paracrine manner, causing a significant impact on signaling pathways, mRNA transcription, and protein expression. The transfer of EVs to target cells, in turn, supports cancer growth, immunosuppression, and metastasis formation. This review focuses exclusively on breast cancer EVs with an emphasis on breast cancer-derived exosomes, keeping in mind that breast cancer-derived EVs share some common physical properties with EVs of other cancers.

[1]  D. Klinke,et al.  Inferring alterations in cell‐to‐cell communication in HER2+ breast cancer using secretome profiling of three cell models , 2014, Biotechnology and bioengineering.

[2]  A. Barberà,et al.  IDO is highly expressed in breast cancer and breast cancer-derived circulating microvesicles and associated to aggressive types of tumors by in silico analysis , 2014, Tumor Biology.

[3]  Jian Jin,et al.  Tumor endothelial expression of P-glycoprotein upon microvesicular transfer of TrpC5 derived from adriamycin-resistant breast cancer cells. , 2014, Biochemical and biophysical research communications.

[4]  M. Michael,et al.  Hypoxic enhancement of exosome release by breast cancer cells , 2012, BMC Cancer.

[5]  Lucy Pigati,et al.  MicroRNAs are exported from malignant cells in customized particles , 2012, Nucleic acids research.

[6]  A. Maraveyas,et al.  Characterization of physical properties of tissue factor–containing microvesicles and a comparison of ultracentrifuge-based recovery procedures , 2014, Journal of extracellular vesicles.

[7]  D. Gygax,et al.  Proteomic analysis of exosome-like vesicles derived from breast cancer cells. , 2012, Anticancer research.

[8]  N. Van Rooijen,et al.  Macrophages mediate inflammation-enhanced metastasis of ovarian tumors in mice. , 2007, Cancer research.

[9]  Wei Tang,et al.  Palmitoylation supports assembly and function of integrin–tetraspanin complexes , 2004, The Journal of cell biology.

[10]  Shirley L. Campbell,et al.  ARF 1 regulates the Rho / MLC pathway to control EGF-dependent breast cancer cell invasion , 2013 .

[11]  M. Mareel,et al.  Bowes melanoma cells secrete heregulin, which can promote aggregation and counteract invasion of human mammary cancer cells , 2005, International journal of cancer.

[12]  T. Whiteside,et al.  Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor-β1 , 2011, Haematologica.

[13]  V. Notario,et al.  The effects of PEDF on cancer biology: mechanisms of action and therapeutic potential , 2013, Nature Reviews Cancer.

[14]  Anthony Fyles,et al.  MicroRNA-301 mediates proliferation and invasion in human breast cancer. , 2011, Cancer research.

[15]  F. Klemm,et al.  Induction and transport of Wnt 5a during macrophage-induced malignant invasion is mediated by two types of extracellular vesicles , 2013, Oncotarget.

[16]  R. Jain,et al.  Emerging strategies for treating brain metastases from breast cancer. , 2015, Cancer cell.

[17]  W. Grizzle,et al.  Contribution of MyD88 to the tumor exosome-mediated induction of myeloid derived suppressor cells. , 2010, The American journal of pathology.

[18]  S. Zhong,et al.  Exosomes from Drug-Resistant Breast Cancer Cells Transmit Chemoresistance by a Horizontal Transfer of MicroRNAs , 2014, PloS one.

[19]  Bart N Lambrecht,et al.  Proteomic analysis of exosomes isolated from human malignant pleural effusions. , 2004, American journal of respiratory cell and molecular biology.

[20]  M. Nugent,et al.  Membrane association of collagenase stimulatory factor(s) from B‐16 melanoma cells , 1987, Journal of cellular biochemistry.

[21]  Gabriele Vargas,et al.  Intercellular transfer of tissue factor via the uptake of tumor-derived microvesicles. , 2012, Thrombosis research.

[22]  Crislyn D'Souza-Schorey,et al.  Microvesicles: mediators of extracellular communication during cancer progression , 2010, Journal of Cell Science.

[23]  H. Mouridsen Adjuvant systemic therapy in breast cancer. , 1993, European journal of cancer.

[24]  G. Semenza,et al.  Hypoxia-inducible factors and RAB22A mediate formation of microvesicles that stimulate breast cancer invasion and metastasis , 2014, Proceedings of the National Academy of Sciences.

[25]  Graça Raposo,et al.  Extracellular vesicles: Exosomes, microvesicles, and friends , 2013, The Journal of cell biology.

[26]  A. Haqqani,et al.  Method for isolation and molecular characterization of extracellular microvesicles released from brain endothelial cells , 2013, Fluids and Barriers of the CNS.

[27]  E. Manson,et al.  Campylobacter jejuni Outer Membrane Vesicles Play an Important Role in Bacterial Interactions with Human Intestinal Epithelial Cells , 2012, Infection and Immunity.

[28]  Jian Zhang,et al.  Exosomal miR-221/222 enhances tamoxifen resistance in recipient ER-positive breast cancer cells , 2014, Breast Cancer Research and Treatment.

[29]  Adwitia Dey,et al.  Ontogeny and Polarization of Macrophages in Inflammation: Blood Monocytes Versus Tissue Macrophages , 2015, Front. Immunol..

[30]  J. Horbańczuk,et al.  Defensins: natural component of human innate immunity. , 2013, Human immunology.

[31]  J. Bharti,et al.  Evaluation of p53, HoxD10, and E-Cadherin Status in Breast Cancer and Correlation with Histological Grade and Other Prognostic Factors , 2014, Journal of oncology.

[32]  S. Fukuda,et al.  Survivin, a cancer target with an emerging role in normal adult tissues , 2006, Molecular Cancer Therapeutics.

[33]  G. Bazzoni,et al.  Specific Association Of CD63 with the VLA-3 and VLA-6 Integrins (*) , 1995, The Journal of Biological Chemistry.

[34]  V. Golubovskaya,et al.  Focal adhesion kinase and cancer. , 2009, Histology and histopathology.

[35]  Giulio Gabbiani,et al.  The stroma reaction myofibroblast: a key player in the control of tumor cell behavior. , 2004, The International journal of developmental biology.

[36]  Jared L. Johnson,et al.  Cancer cell-derived microvesicles induce transformation by transferring tissue transglutaminase and fibronectin to recipient cells , 2011, Proceedings of the National Academy of Sciences.

[37]  R. M. Pope,et al.  Biochemical and biological characterization of exosomes containing prominin-1/CD133 , 2013, Molecular Cancer.

[38]  A. Clayton,et al.  Exosomes and the MICA-NKG2D system in cancer. , 2005, Blood cells, molecules & diseases.

[39]  K. Honn,et al.  Thrombin enhances tumor cell adhesive and metastatic properties via increased αIIbβ3 expression on the cell surface , 1992 .

[40]  F. Hanisch,et al.  Proteomics of MUC1‐containing lipid rafts from plasma membranes and exosomes of human breast carcinoma cells MCF‐7 , 2009, Proteomics.

[41]  Shengbing Huang,et al.  The Role of Autophagy in Cancer: Therapeutic Implications , 2011, Molecular Cancer Therapeutics.

[42]  J. Dogné,et al.  Thrombin generation assay and transmission electron microscopy: a useful combination to study tissue factor-bearing microvesicles , 2013, Journal of extracellular vesicles.

[43]  G. Nickenig,et al.  MicroRNA Expression in Circulating Microvesicles Predicts Cardiovascular Events in Patients With Coronary Artery Disease , 2014, Journal of the American Heart Association.

[44]  M. Pittet,et al.  Molecular Pathways Molecular Pathways : Tumor-DerivedMicrovesicles andTheir Interactions with Immune Cells In Vivo , 2013 .

[45]  Simon C Watkins,et al.  Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. , 2004, Blood.

[46]  Shazib Pervaiz,et al.  Annexin 1: the new face of an old molecule , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[47]  L. Borsig,et al.  Cancer Cell Adhesion and Metastasis: Selectins, Integrins, and the Inhibitory Potential of Heparins , 2012, International journal of cell biology.

[48]  H. Geuze,et al.  Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. , 2000, Journal of cell science.

[49]  S. Riddell,et al.  Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC induced on virus-infected cells. , 2001, Nature immunology.

[50]  O. Janssen,et al.  Shedding of endogenous MHC class I‐related chain molecules A and B from different human tumor entities: Heterogeneous involvement of the “a disintegrin and metalloproteases” 10 and 17 , 2013, International journal of cancer.

[51]  C. Kuijl,et al.  MICA engagement by human Vgamma2Vdelta2 T cells enhances their antigen-dependent effector function. , 2001, Immunity.

[52]  R. Muschel,et al.  Coagulation and metastasis: what does the experimental literature tell us? , 2013, British journal of haematology.

[53]  C. Emiliani,et al.  Signaling Pathways in Exosomes Biogenesis, Secretion and Fate , 2013, Genes.

[54]  L. O’Driscoll,et al.  Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells. , 2013, European journal of cancer.

[55]  J. Gruenberg,et al.  ALIX and the multivesicular endosome: ALIX in Wonderland. , 2014, Trends in cell biology.

[56]  Paul Harrison,et al.  Classification, Functions, and Clinical Relevance of Extracellular Vesicles , 2012, Pharmacological Reviews.

[57]  D. Noonan,et al.  The α3β1 integrin is associated with mammary carcinoma cell metastasis, invasion, and gelatinase B (mmp‐9) activity , 2000 .

[58]  William E. Grizzle,et al.  Murine Mammary Carcinoma Exosomes Promote Tumor Growth by Suppression of NK Cell Function1 , 2006, The Journal of Immunology.

[59]  K. Honn,et al.  Thrombin enhances tumor cell adhesive and metastatic properties via increased alpha IIb beta 3 expression on the cell surface. , 1992, Thrombosis research.

[60]  J. Sixma,et al.  Activated Platelets Release Two Types of Membrane Vesicles: Microvesicles by Surface Shedding and Exosomes Derived From Exocytosis of Multivesicular Bodies and -Granules , 1999 .

[61]  Hui Li,et al.  Upregulation of miR-301a correlates with poor prognosis in triple-negative breast cancer , 2014, Medical Oncology.

[62]  Linda J Pike,et al.  Mechanics of EGF Receptor/ErbB2 kinase activation revealed by luciferase fragment complementation imaging , 2011, Proceedings of the National Academy of Sciences.

[63]  Josiah Ochieng,et al.  Detachment of Breast Tumor Cells Induces Rapid Secretion of Exosomes Which Subsequently Mediate Cellular Adhesion and Spreading , 2011, PloS one.

[64]  C. Stipp,et al.  The CD9/CD81 Tetraspanin Complex and Tetraspanin CD151 Regulate α3β1 Integrin-Dependent Tumor Cell Behaviors by Overlapping but Distinct Mechanisms , 2013, PloS one.

[65]  W T Bellamy,et al.  P-glycoproteins and multidrug resistance. , 1996, Annual review of pharmacology and toxicology.

[66]  T. Spies,et al.  MICA Engagement by Human Vγ2Vδ2 T Cells Enhances Their Antigen-Dependent Effector Function , 2001 .

[67]  P. Stricker,et al.  Growth factor involvement in progression of prostate cancer. , 1998, Clinical chemistry.

[68]  M. Symons,et al.  Implications of Rho GTPase Signaling in Glioma Cell Invasion and Tumor Progression , 2013, Front. Oncol..

[69]  G. Fasola,et al.  Pattern of metastasis and outcome in patients with breast cancer , 2015, Clinical & Experimental Metastasis.

[70]  Markus Munz,et al.  The emerging role of EpCAM in cancer and stem cell signaling. , 2009, Cancer research.

[71]  Cicek Gercel-Taylor,et al.  MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. , 2008, Gynecologic oncology.

[72]  M. Campiglio,et al.  Potential role of HER2‐overexpressing exosomes in countering trastuzumab‐based therapy , 2012, Journal of cellular physiology.

[73]  G. Odorizzi The multiple personalities of Alix , 2006, Journal of Cell Science.

[74]  Salma Khan,et al.  Early diagnostic value of survivin and its alternative splice variants in breast cancer , 2014, BMC Cancer.

[75]  F. Almeida,et al.  Structural basis for the interaction of human β-defensin 6 and its putative chemokine receptor CCR2 and breast cancer microvesicles. , 2013, Journal of molecular biology.

[76]  Aled Clayton,et al.  Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids , 2006, Current protocols in cell biology.

[77]  J. Rak,et al.  Microvesicles as mediators of intercellular communication in cancer—the emerging science of cellular ‘debris’ , 2011, Seminars in Immunopathology.

[78]  A. Molinari,et al.  Microenvironmental pH Is a Key Factor for Exosome Traffic in Tumor Cells* , 2009, The Journal of Biological Chemistry.

[79]  M. Kortylewski,et al.  Macrophage immunomodulation by breast cancer-derived exosomes requires Toll-like receptor 2-mediated activation of NF-κB , 2014, Scientific Reports.

[80]  N. Normanno,et al.  Epidermal growth factor receptor (EGFR) signaling in cancer. , 2006, Gene.

[81]  P. Zheng,et al.  CD24: from A to Z , 2010, Cellular and Molecular Immunology.

[82]  I. Kurochkin,et al.  Characterization of RNA in exosomes secreted by human breast cancer cell lines using next-generation sequencing , 2013, PeerJ.

[83]  Luigi Biancone,et al.  Exosomes/microvesicles as a mechanism of cell-to-cell communication. , 2010, Kidney international.

[84]  A. Ridley,et al.  Rho GTPases in cancer cell biology , 2008, FEBS letters.

[85]  A. Jemal,et al.  Cancer statistics, 2015 , 2015, CA: a cancer journal for clinicians.

[86]  Sun-Young Chang,et al.  Blockade of Myd88 signaling induces antitumor effects by skewing the immunosuppressive function of myeloid‐derived suppressor cells , 2013, International journal of cancer.

[87]  P. Hersey,et al.  Regulation of tumor cell motility and migration by CD63 in a human melanoma cell line. , 1997, Journal of immunology.

[88]  E. Cisneros,et al.  Analysis of exosome release and its prognostic value in human colorectal cancer , 2012, Genes, chromosomes & cancer.

[89]  G. Ayers,et al.  Amphiregulin Exosomes Increase Cancer Cell Invasion , 2011, Current Biology.

[90]  George A Calin,et al.  Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. , 2014, Cancer cell.

[91]  William E. Grizzle,et al.  Tumor Exosomes Inhibit Differentiation of Bone Marrow Dendritic Cells1 , 2007, The Journal of Immunology.

[92]  G. Hortobagyi,et al.  Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis. , 2004, Cancer cell.

[93]  S. Chakrabarty,et al.  Proliferation of human colon cancer cells: Role of epidermal growth factor and transforming growth factorα , 1992, International journal of cancer.

[94]  L. Lanier,et al.  Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family , 2001, Immunogenetics.

[95]  Gladys N. Nangami,et al.  Fetuin-A associates with histones intracellularly and shuttles them to exosomes to promote focal adhesion assembly resulting in rapid adhesion and spreading in breast carcinoma cells. , 2014, Experimental cell research.

[96]  K. Shedden,et al.  Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles. , 2003, Cancer research.

[97]  Zacharie Segaoula,et al.  Tie2-dependent deletion of α6 integrin subunit in mice reduces tumor growth and angiogenesis. , 2014, International journal of oncology.

[98]  Ylva Ivarsson,et al.  Syndecan–syntenin–ALIX regulates the biogenesis of exosomes , 2012, Nature Cell Biology.

[99]  Yasumasa Kato,et al.  Acidic extracellular microenvironment and cancer , 2013, Cancer Cell International.

[100]  E. Salazar,et al.  Elevated concentration of microvesicles isolated from peripheral blood in breast cancer patients. , 2013, Archives of medical research.

[101]  S. Zhong,et al.  Exosomes from docetaxel-resistant breast cancer cells alter chemosensitivity by delivering microRNAs , 2014, Tumor Biology.

[102]  D. Wong,et al.  Breast Cancer Exosome-like Microvesicles and Salivary Gland Cells Interplay Alters Salivary Gland Cell-Derived Exosome-like Microvesicles In Vitro , 2012, PloS one.

[103]  R. Theriault,et al.  Increased levels of α6 integrins are associated with the metastatic phenotype of human breast cancer cells , 1999, Clinical & Experimental Metastasis.

[104]  Judith Klumperman,et al.  Trafficking and function of the tetraspanin CD63. , 2009, Experimental cell research.

[105]  M. Piccart,et al.  Adjuvant systemic therapy in breast cancer: quo vadis? , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[106]  D. Richardson,et al.  P-glycoprotein Mediates Drug Resistance via a Novel Mechanism Involving Lysosomal Sequestration* , 2013, The Journal of Biological Chemistry.

[107]  Y. Lu,et al.  The expression of BTG1 is downregulated in NSCLC and possibly associated with tumor metastasis , 2014, Tumor Biology.

[108]  Robert S Negrin,et al.  Role of NKG2D signaling in the cytotoxicity of activated and expanded CD8+ T cells. , 2004, Blood.

[109]  C. Barbas,et al.  Alphav integrins mediate adhesion and migration of breast carcinoma cell lines. , 1998, Clinical & experimental metastasis.

[110]  H. Larjava,et al.  Expression of integrins and basement membrane components by wound keratinocytes. , 1993, The Journal of clinical investigation.

[111]  Genevieve DeMaria,et al.  Characterization of exosome‐like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[112]  Holger Sültmann,et al.  Loss of EpCAM expression in breast cancer derived serum exosomes: role of proteolytic cleavage. , 2011, Gynecologic oncology.

[113]  Xu-wen Liu,et al.  Identification of CD63 as a tissue inhibitor of metalloproteinase‐1 interacting cell surface protein , 2006, The EMBO journal.

[114]  A. Jemal,et al.  Cancer treatment and survivorship statistics, 2014 , 2014, CA: a cancer journal for clinicians.

[115]  Yi Tang,et al.  Tumor-stroma interaction: positive feedback regulation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN. , 2004, Molecular cancer research : MCR.

[116]  J. Hurley,et al.  Get on the exosome bus with ALIX , 2012, Nature Cell Biology.

[117]  F. Esteva,et al.  Her2-positive breast cancer: herceptin and beyond. , 2008, European journal of cancer.

[118]  Tae-Min Kim,et al.  CD63 as a biomarker for predicting the clinical outcomes in adenocarcinoma of lung. , 2007, Lung cancer.

[119]  Jun Zhang,et al.  Exosomes mediate drug resistance transfer in MCF-7 breast cancer cells and a probable mechanism is delivery of P-glycoprotein , 2014, Tumor Biology.

[120]  D. Hawke,et al.  Molecular characterization of exosome-like vesicles from breast cancer cells , 2014, BMC Cancer.

[121]  U. Welsch,et al.  Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC , 2011, Cancer Immunology, Immunotherapy.

[122]  Elaine C. Campbell,et al.  Monitoring the Rab27 associated exosome pathway using nanoparticle tracking analysis. , 2013, Experimental cell research.

[123]  Jung Ah Cho,et al.  Exosomes from breast cancer cells can convert adipose tissue-derived mesenchymal stem cells into myofibroblast-like cells. , 2011, International journal of oncology.

[124]  Massimo Spada,et al.  High Levels of Exosomes Expressing CD63 and Caveolin-1 in Plasma of Melanoma Patients , 2009, PloS one.

[125]  D. Goeddel,et al.  Identification of Heregulin, a Specific Activator of p185erbB2 , 1992, Science.

[126]  Sandra Barth,et al.  Autophagy: cellular and molecular mechanisms , 2010, The Journal of pathology.

[127]  P. Xie,et al.  M2-polarized tumor-associated macrophages promoted epithelial–mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway , 2013, Laboratory Investigation.

[128]  J. Westermarck,et al.  Regulation of matrix metalloproteinase expression in tumor invasion , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[129]  Gang Wang,et al.  Alpha-enolase as a potential cancer prognostic marker promotes cell growth, migration, and invasion in glioma , 2014, Molecular Cancer.

[130]  S. Tangutoori,et al.  PARP inhibitors: A new era of targeted therapy. , 2015, Maturitas.

[131]  Alberto Mantovani,et al.  Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. , 2006, European journal of cancer.

[132]  Z. Shao,et al.  Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in metastatic breast cancer , 2015, Journal of Experimental & Clinical Cancer Research.

[133]  J. Lötvall,et al.  Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes , 2013, Journal of extracellular vesicles.

[134]  G. Watkins,et al.  Decreased Pigment Epithelium–Derived Factor Expression in Human Breast Cancer Progression , 2006, Clinical Cancer Research.

[135]  E. Salazar,et al.  Extracellular vesicles from women with breast cancer promote an epithelial-mesenchymal transition-like process in mammary epithelial cells MCF10A , 2015, Tumor Biology.

[136]  S. Barsky,et al.  A novel human xenograft model of inflammatory breast cancer. , 1999, Cancer research.

[137]  J. Ochieng,et al.  Annexin A6 contributes to the invasiveness of breast carcinoma cells by influencing the organization and localization of functional focal adhesions. , 2011, Experimental cell research.

[138]  F. Montemurro,et al.  HER2-positive metastatic breast cancer: a changing scenario. , 2015, Critical reviews in oncology/hematology.

[139]  C. Shuler,et al.  Regulation of tumor cell invasion by extracellular matrix. , 1999, Histology and histopathology.

[140]  S. Dutta,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 , 2014, PloS one.

[141]  D. Hedley,et al.  The clinical significance of hypoxia in human cancers. , 2015, Seminars in nuclear medicine.

[142]  Weiying Zhou,et al.  Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. , 2014, Cancer cell.

[143]  José A López,et al.  Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. , 2005, Blood.

[144]  C. Scharf,et al.  Tumor-derived microvesicles mediate human breast cancer invasion through differentially glycosylated EMMPRIN , 2014, Journal of molecular cell biology.

[145]  Shinobu Ueda,et al.  Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor MicroRNA to Breast Cancer Cells. , 2013, Molecular therapy : the journal of the American Society of Gene Therapy.

[146]  J. Baselga,et al.  Unconventional Secretion is a Major Contributor of Cancer Cell Line Secretomes* , 2012, Molecular & Cellular Proteomics.

[147]  Jian Song,et al.  A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. , 2014, Biomaterials.

[148]  Y. Mo,et al.  Exosome-mediated transfer of miR-10b promotes cell invasion in breast cancer , 2014, Molecular Cancer.

[149]  Carmen Visus,et al.  Tumor-Derived Microvesicles Promote Regulatory T Cell Expansion and Induce Apoptosis in Tumor-Reactive Activated CD8+ T Lymphocytes1 , 2009, The Journal of Immunology.

[150]  W. Grizzle,et al.  Curcumin reverses breast tumor exosomes mediated immune suppression of NK cell tumor cytotoxicity. , 2007, Biochimica et biophysica acta.

[151]  Y. Jeon,et al.  Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumor-associated macrophage infiltration and M2 polarization , 2013, BMC Cancer.

[152]  S. Mathivanan,et al.  ExoCarta: A compendium of exosomal proteins and RNA , 2009, Proteomics.

[153]  Caroline Gilbert,et al.  Syncytin proteins incorporated in placenta exosomes are important for cell uptake and show variation in abundance in serum exosomes from patients with preeclampsia , 2014, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[154]  Robert M Hoffman,et al.  Imaging exosome transfer from breast cancer cells to stroma at metastatic sites in orthotopic nude-mouse models. , 2013, Advanced drug delivery reviews.

[155]  F. Petrucci,et al.  Exosome Release and Low pH Belong to a Framework of Resistance of Human Melanoma Cells to Cisplatin , 2014, PloS one.

[156]  D. Santini,et al.  PPARγ and RXR Ligands Disrupt the Inflammatory Cross‐talk in the Hypoxic Breast Cancer Stem Cells Niche , 2014, Journal of cellular physiology.

[157]  Shirley L. Campbell,et al.  ARF1 regulates the Rho/MLC pathway to control EGF-dependent breast cancer cell invasion , 2014, Molecular biology of the cell.

[158]  D. Noonan,et al.  The α3β1 Integrin Is Involved in Melanoma Cell Migration and Invasion , 1995 .

[159]  Chuanshu Huang,et al.  Inflammation, a Key Event in Cancer Development , 2006, Molecular Cancer Research.

[160]  T. Visakorpi,et al.  Different gDNA Content in the Subpopulations of Prostate Cancer Extracellular Vesicles: Apoptotic Bodies, Microvesicles, and Exosomes , 2014, The Prostate.

[161]  H R Büller,et al.  Cell-derived microvesicles and cancer. , 2009, The Netherlands journal of medicine.

[162]  A. Poliakov,et al.  Induction of myeloid‐derived suppressor cells by tumor exosomes , 2009, International journal of cancer.

[163]  A. Tedgui,et al.  Microvesicles as Cell–Cell Messengers in Cardiovascular Diseases , 2014, Circulation research.

[164]  W. Grizzle,et al.  Tumor cell cross talk with tumor-associated leukocytes leads to induction of tumor exosomal fibronectin and promotes tumor progression. , 2012, The American journal of pathology.

[165]  Xu-wen Liu,et al.  Novel functions of TIMPs in cell signaling , 2006, Cancer and Metastasis Reviews.

[166]  V. Paradis,et al.  Endothelial cell-derived microparticles loaded with iron oxide nanoparticles: feasibility of MR imaging monitoring in mice. , 2012, Radiology.

[167]  M. Trivella,et al.  Characterization of secreted vesicles from vascular smooth muscle cells. , 2014, Molecular bioSystems.

[168]  A. Redig,et al.  Breast cancer as a systemic disease: a view of metastasis , 2013, Journal of internal medicine.