Skip to main content Accessibility help
Hostname: page-component-99c86f546-t82dr Total loading time: 0.926 Render date: 2021-12-01T10:16:22.413Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": true, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true, "newUsageEvents": true }

17 - Cell-Derived Microvesicles and Metastasis


Published online by Cambridge University Press:  05 June 2012

Hector Peinado
Weill Cornell Medical College, United States
Bethan Psaila
Imperial College London, United Kingdom
David Lyden
University of California at Los Angeles, United States
David Lyden
Weill Cornell Medical College, New York
Danny R. Welch
Weill Cornell Medical College, New York
Bethan Psaila
Imperial College of Medicine, London
Get access



Cell-membrane–derived vesicles are spherical membrane fragments shed by several cell types during their normal functioning. In the past, this “cellular dust” was overlooked and dismissed as insignificant debris. However, a role for these particles in physiological processes such as coagulation, immune regulation, intercellular crosstalk, and molecule delivery has now been established. In addition, increasing attention has been focused on the role of membrane vesicles in pathological processes, particularly as a cell–cell communication system that promotes tumorigenesis and malignant progression. This chapter outlines the complex interplay between membrane vesicles derived from tumor cells and host cells. Although molecular pathways involved in membrane vesicle biology and function have not been delineated, therapeutic manipulation of membrane-derived vesicles in patients with cancer has already entered the clinical arena. In the future, targeting membrane-derived vesicles may prove to be an effective approach in reducing morbidity and mortality of advanced malignancy, particularly in metastatic disease.


Membrane-derived vesicles have been broadly classified into two types based on their size and mechanism of release. Microvesicles are small, heterogeneous membrane particles between 100 nm and 1 μm in size that are released from the intracellular endosome by membrane blebbing. In contrast, exosomes are even smaller membrane particles (30 nm–100 nm) thought to originate from multivesicular bodies during endocytosis. Although membrane vesicles derived from cells of hematopoietic origin were the first to be identified, including those released from B and T lymphocytes, platelets, dendritic cells, mast cells, and reticulocytes, recent evidence indicates that nonhematopoietic cell types, such as neurons, epithelial cells, and tumor cells, can also shed microvesicles.

Cancer Metastasis
Biologic Basis and Therapeutics
, pp. 191 - 198
Publisher: Cambridge University Press
Print publication year: 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


Pilzer, D, Gasser, O, Moskovich, O, Schifferli, JA, Fishelson, Z (2005) Emission of membrane vesicles: roles in complement resistance, immunity and cancer. Springer Semin Immunopathol. 27: 375–87.CrossRefGoogle ScholarPubMed
Ratajczak, J, Wysoczynski, M, Hayek, F, Janowska-Wieczorek, A, Ratajczak, MZ (2006) Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia. 20: 1487–95.CrossRefGoogle ScholarPubMed
Lakkaraju, A, Rodriguez-Boulan, E (2008) Itinerant exosomes: emerging roles in cell and tissue polarity. Trends Cell Biol. 18: 199–209.CrossRefGoogle ScholarPubMed
Niel, G, Porto-Carreiro, I, Simoes, S, Raposo, G (2006) Exosomes: a common pathway for a specialized function. J Biochem. 140: 13–21.CrossRefGoogle ScholarPubMed
Simak, J, Gelderman, MP (2006) Cell membrane microparticles in blood and blood products: potentially pathogenic agents and diagnostic markers. Transfus Med Rev. 20: 1–26.CrossRefGoogle ScholarPubMed
Poste, G, Nicolson, GL (1980) Arrest and metastasis of blood-borne tumor cells are modified by fusion of plasma membrane vesicles from highly metastatic cells. Proc Natl Acad Sci U S A 77: 399–403.CrossRefGoogle ScholarPubMed
Dolo, V, Adobati, E, Canevari, S, Picone, MA, Vittorelli, ML (1995) Membrane vesicles shed into the extracellular medium by human breast carcinoma cells carry tumor-associated surface antigens. Clin Exp Metastasis. 13: 277–86.CrossRefGoogle ScholarPubMed
Faure, J et al. (2006) Exosomes are released by cultured cortical neurones. Mol Cell Neurosci. 31: 642–8.CrossRefGoogle ScholarPubMed
Niel, G et al. (2001) Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology. 121: 337–49.CrossRefGoogle ScholarPubMed
Thery, C, Zitvogel, L, Amigorena, S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2: 569–79.CrossRefGoogle ScholarPubMed
Fevrier, B, Raposo, G (2004) Exosomes: endosomal-derived vesicles shipping extracellular messages. Curr Opin Cell Biol. 16: 415–21.CrossRefGoogle ScholarPubMed
Iero, M et al. (2008) Tumor-released exosomes and their implications in cancer immunity. Cell Death Differ. 15: 80–8.CrossRefGoogle Scholar
Greco, V, Hannus, M, Eaton, S (2001) Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell. 106: 633–45.CrossRefGoogle ScholarPubMed
Eaton, S (2006) Release and trafficking of lipid-linked morphogens. Curr Opin Genet Dev. 16: 17–22.CrossRefGoogle ScholarPubMed
Baj-Krzyworzeka, M et al. (2006) Tumor-derived microvesicles carry several surface determinants and mRNA of tumor cells and transfer some of these determinants to monocytes. Cancer Immunol Immunother. 55: 808–18.CrossRefGoogle Scholar
Janowska-Wieczorek, A et al. (2001) Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment. Blood. 98: 3143–9.CrossRefGoogle ScholarPubMed
Ratajczak, J et al. (2006) Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia. 20: 847–56.CrossRefGoogle ScholarPubMed
Giusti, I et al. (2008) Cathepsin B mediates the pH-dependent proinvasive activity of tumor-shed microvesicles. Neoplasia. 10: 481–8.CrossRefGoogle ScholarPubMed
Dolo, V et al. (1998) 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. 58: 4468–74.Google Scholar
Dolo, V et al. (1999) Matrix-degrading proteinases are shed in membrane vesicles by ovarian cancer cells in vivo and in vitro. Clin Exp Metastasis. 17: 131–40.CrossRefGoogle ScholarPubMed
Kim, CW et al. (2002) Extracellular membrane vesicles from tumor cells promote angiogenesis via sphingomyelin. Cancer Res. 62: 6312–7.Google ScholarPubMed
Kim, HK et al. (2003) 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. 39: 184–91.CrossRefGoogle ScholarPubMed
Millimaggi, D et al. (2007) Tumor vesicle-associated CD147 modulates the angiogenic capability of endothelial cells. Neoplasia. 9: 349–57.CrossRefGoogle ScholarPubMed
Dolo, V, Pizzurro, P, Ginestra, A, Vittorelli, ML (1995) Inhibitory effects of vesicles shed by human breast carcinoma cells on lymphocyte 3H-thymidine incorporation, are neutralised by anti TGF-beta antibodies. J Submicrosc Cytol Pathol. 27: 535–41.Google ScholarPubMed
Andre, F et al. (2002) Tumor-derived exosomes: a new source of tumor rejection antigens. Vaccine. 20 Suppl4: A28–31.CrossRefGoogle ScholarPubMed
Andreola, G et al. (2002) Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. J Exp Med. 195: 1303–16.CrossRefGoogle ScholarPubMed
Wieckowski, E, Whiteside, TL (2006) Human tumor-derived vs dendritic cell-derived exosomes have distinct biologic roles and molecular profiles. Immunol Res. 36: 247–54.CrossRefGoogle ScholarPubMed
Kim, JW et al. (2005) Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clin Cancer Res. 11: 1010–20.Google ScholarPubMed
Huber, V et al. (2005) Human colorectal cancer cells induce T-cell death through release of proapoptotic microvesicles: role in immune escape. Gastroenterology. 128: 1796–804.CrossRefGoogle ScholarPubMed
Abrahams, VM et al. (2003) Epithelial ovarian cancer cells secrete functional Fas ligand. Cancer Res. 63: 5573–81.Google ScholarPubMed
Valenti, R et al. (2006) Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-beta-mediated suppressive activity on T lymphocytes. Cancer Res. 66: 9290–8.CrossRefGoogle ScholarPubMed
Shedden, K, Xie, XT, Chandaroy, P, Chang, YT, Rosania, GR (2003) Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles. Cancer Res. 63: 4331–7.Google ScholarPubMed
Valenti, R et al. (2007) Tumor-released microvesicles as vehicles of immunosuppression. Cancer Res. 67: 2912–5.CrossRefGoogle ScholarPubMed
Choi, DS et al. (2007) Proteomic analysis of microvesicles derived from human colorectal cancer cells. J Proteome Res. 6: 4646–55.CrossRefGoogle ScholarPubMed
Hegmans, JP et al. (2004) Proteomic analysis of exosomes secreted by human mesothelioma cells. Am J Pathol. 164: 1807–15.CrossRefGoogle ScholarPubMed
Lerner, MP, Lucid, SW, Wen, GJ, Nordquist, RE (1983) Selected area membrane shedding by tumor cells. Cancer Lett. 20: 125–30.CrossRefGoogle ScholarPubMed
Ginestra, A et al. (1998) The amount and proteolytic content of vesicles shed by human cancer cell lines correlates with their in vitro invasiveness. Anticancer Res. 18: 3433–7.Google ScholarPubMed
Mayer, C et al. (2004) Release of cell fragments by invading melanoma cells. Eur J Cell Biol. 83: 709–15.CrossRefGoogle ScholarPubMed
Sun, J, Hemler, ME (2001) Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions. Cancer Res. 61: 2276–81.Google ScholarPubMed
Gutwein, P et al. (2003) ADAM10-mediated cleavage of L1 adhesion molecule at the cell surface and in released membrane vesicles. FASEB J. 17: 292–4.CrossRefGoogle ScholarPubMed
Gesierich, S, Berezovskiy, I, Ryschich, E, Zoller, M (2006) Systemic induction of the angiogenesis switch by the tetraspanin D6.1A/CO-029. Cancer Res. 66: 7083–94.CrossRefGoogle ScholarPubMed
Sidhu, SS, Mengistab, AT, Tauscher, AN, LaVail, J, Basbaum, C (2004) The microvesicle as a vehicle for EMMPRIN in tumor-stromal interactions. Oncogene. 23: 956–63.CrossRefGoogle ScholarPubMed
Skog, J et al. (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumor growth and provide diagnostic biomarkers. Nat Cell Biol. 10: 1470–6.CrossRefGoogle ScholarPubMed
Al-Nedawi, K et al. (2008) Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumor cells. Nat Cell Biol. 10: 619–24.CrossRefGoogle Scholar
Dahiya, R et al. (1992) Metastasis-associated alterations in phospholipids and fatty acids of human prostatic adenocarcinoma cell lines. Biochem Cell Biol. 70: 548–54.CrossRefGoogle ScholarPubMed
Schaffner, F, Ruf, W (2008) Tissue factor and protease-activated receptor signaling in cancer. Semin Thromb Hemost. 34: 147–53.CrossRefGoogle Scholar
Sahni, A, Simpson-Haidaris, PJ, Sahni, SK, Vaday, GG, Francis, CW (2008) Fibrinogen synthesized by cancer cells augments the proliferative effect of fibroblast growth factor-2 (FGF-2). J Thromb Haemost. 6: 176–83.CrossRefGoogle ScholarPubMed
Janowska-Wieczorek, A, Marquez-Curtis, , Wysoczynski, M, Ratajczak, MZ (2006) Enhancing effect of platelet-derived microvesicles on the invasive potential of breast cancer cells. Transfusion. 46: 1199–209.CrossRefGoogle ScholarPubMed
Janowska-Wieczorek, A et al. (2005) Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer. 113: 752–60.CrossRefGoogle ScholarPubMed
Kanazawa, S et al. (2003) Monocyte-derived microparticles may be a sign of vascular complication in patients with lung cancer. Lung Cancer. 39: 145–9.CrossRefGoogle ScholarPubMed
Kaplan, RN et al. (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 438: 820–7.CrossRefGoogle ScholarPubMed
Wels, J, Kaplan, RN, Rafii, S, Lyden, D (2008) Migratory neighbors and distant invaders: tumor-associated niche cells. Genes Dev. 22: 559–74.CrossRefGoogle ScholarPubMed
Gao, D et al. (2008) Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science. 319: 195–8.CrossRefGoogle ScholarPubMed
Chaput, N, Schartz, NE, Andre, F, Zitvogel, L (2003) Exosomes for immunotherapy of cancer. Adv Exp Med Biol. 532: 215–21.CrossRefGoogle ScholarPubMed
Chaput, N et al. (2006) Dendritic cell derived-exosomes: biology and clinical implementations. J Leukoc Biol. 80: 471–8.CrossRefGoogle ScholarPubMed
Delcayre, A, Shu, H, Pecq, JB (2005) Dendritic cell-derived exosomes in cancer immunotherapy: exploiting nature's antigen delivery pathway. Expert Rev Anticancer Ther. 5: 537–47.CrossRefGoogle ScholarPubMed
Andre, F et al. (2004) Exosomes as potent cell-free peptide-based vaccine. I. Dendritic cell-derived exosomes transfer functional MHC class I/peptide complexes to dendritic cells. J Immunol. 172: 2126–36.CrossRefGoogle ScholarPubMed
Thery, C et al. (2002) Indirect activation of naive CD4+ T cells by dendritic cell-derived exosomes. Nat Immunol. 3: 1156–62.CrossRefGoogle ScholarPubMed
Utsugi-Kobukai, S, Fujimaki, H, Hotta, C, Nakazawa, M, Minami, M (2003) MHC class I-mediated exogenous antigen presentation by exosomes secreted from immature and mature bone marrow derived dendritic cells. Immunol Lett. 89: 125–31.CrossRefGoogle ScholarPubMed
Segura, E, Amigorena, S, Thery, C (2005) Mature dendritic cells secrete exosomes with strong ability to induce antigen-specific effector immune responses. Blood Cells Mol Dis. 35: 89–93.CrossRefGoogle ScholarPubMed
Matsumoto, K et al. (2004) Exosomes secreted from monocyte-derived dendritic cells support in vitro naive CD4+ T cell survival through NF-(kappa)B activation. Cell Immunol. 231: 20–9.CrossRefGoogle ScholarPubMed
Segura, E et al. (2005) ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming. Blood. 106: 216–23.CrossRefGoogle ScholarPubMed
Hsu, DH et al. (2003) Exosomes as a tumor vaccine: enhancing potency through direct loading of antigenic peptides. J Immunother. 26: 440–50.CrossRefGoogle ScholarPubMed
Zitvogel, L et al. (1998) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med. 4: 594–600.CrossRefGoogle ScholarPubMed
Taieb, J et al. (2006) Chemoimmunotherapy of tumors: cyclophosphamide synergizes with exosome based vaccines. J Immunol. 176: 2722–9.CrossRefGoogle ScholarPubMed
Escudier, B et al. (2005) Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first phase I clinical trial. J Transl Med. 3: 10.CrossRefGoogle Scholar
Loveland, BE et al. (2006) Mannan-MUC1-pulsed dendritic cell immunotherapy: a phase I trial in patients with adenocarcinoma. Clin Cancer Res. 12: 869–77.CrossRefGoogle ScholarPubMed
Mackensen, A et al. (2000) Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells. Int J Cancer. 86: 385–92.3.0.CO;2-T>CrossRefGoogle ScholarPubMed
Morse, MA et al. (2005) A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J Transl Med. 3: 9.CrossRefGoogle ScholarPubMed
Mu, LJ et al. (2005) Immunotherapy with allotumor mRNA-transfected dendritic cells in androgen-resistant prostate cancer patients. Br J Cancer. 93: 749–56.CrossRefGoogle Scholar
Hao, S, Bai, O, Yuan, J, Qureshi, M, Xiang, J (2006) Dendritic cell-derived exosomes stimulate stronger CD8+ CTL responses and antitumor immunity than tumor cell-derived exosomes. Cell Mol Immunol. 3: 205–11.Google ScholarPubMed
Andre, F et al. (2002) Malignant effusions and immunogenic tumor-derived exosomes. Lancet. 360: 295–305.CrossRefGoogle Scholar
Ginestra, A, Miceli, D, Dolo, V, Romano, FM, Vittorelli, ML (1999) Membrane vesicles in ovarian cancer fluids: a new potential marker. Anticancer Res. 19: 3439–45.Google ScholarPubMed
Taylor, DD, Gercel-Taylor, C (2008) MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. 110: 13–21.CrossRefGoogle ScholarPubMed
Wolfers, J et al. (2001) Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med. 7: 297–303.CrossRefGoogle ScholarPubMed
Dai, S et al. (2008) Phase I clinical trial of autologous asrefs-derived exosomes combined with GM-CSF for colorectal cancer. Mol Ther. 16: 782–90.CrossRefGoogle ScholarPubMed
Ichim, TE et al. (2008) Exosomes as a tumor immune escape mechanism: possible therapeutic implications. J Transl Med. 6: 37.CrossRefGoogle ScholarPubMed

Send book to Kindle

To send this book to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats

Send book to Dropbox

To send content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about sending content to Dropbox.

Available formats

Send book to Google Drive

To send content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about sending content to Google Drive.

Available formats