Skip to main content

Exosomes

  • Protocol
Functional Proteomics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 484))

Abstract

Exosomes are small natural membrane vesicles released by a wide variety of cell types into the extracellular compartment by exocytosis. The biological functions of exosomes are only slowly unveiled, but it is clear that they serve to remove unnecessary cellular proteins (e.g., during reticulocyte maturation) and act as intercellular messengers because they fuse easily with the membranes of neighboring cells, delivering membrane and cytoplasmic proteins from one cell to another. Recent findings suggests that cell-derived vesicles (exosomes are also named membranous vesicles or microvesicles) could also induce immune tolerance, suppression of natural killer cell function, T cell apoptosis, or metastasis. For example, by secreting exosomes, tumors may be able to accomplish the loss of those antigens that may be immunogenic and capable of signaling to immune cells as well as inducing dysfunction or death of immune effector cells. On the other hand, dendritic cell-derived exosomes have the potential to be an attractive poweful immunotherapeutic tool combining the antitumor activity of dendritic cells with the advantages of a cell-free vehicle. Although the full understanding of the significance of exosomes requires additional studies, these membrane vesicles could become a new important component in orchestrating responses between cells.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Denzer, K., Kleijmeer, M. J., Heijnen, H. F., Stoorvogel, W., and Geuze, H. J. (2000) Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J. Cell Sci. 113, 3365–3374.

    PubMed  CAS  Google Scholar 

  2. Johnstone, R. M., Adam, M., Hammond, J. R., Orr, L., and Turbide, C. (1987) Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem. 262, 9412–9420.

    PubMed  CAS  Google Scholar 

  3. Ratajczak, J., Wysoczynski, M., Hayek, F., Janowska-Wieczorek, A., and Ratajczak, M. Z. (2006) Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia 20, 1487–1495.

    Article  PubMed  CAS  Google Scholar 

  4. Peche, H., Heslan, M., Usal, C., Amigorena, S., and Cuturi, M. C. (2003) Presentation of donor major histocompatibility complex antigens by bone marrow dendritic cell-derived exosomes modulates allograft rejection. Transplantation 76, 1503–1510.

    Article  PubMed  CAS  Google Scholar 

  5. Taylor, D. D. and Gercel-Taylor, C. (2005) Tumour-derived exosomes and their role in cancer-associated T-cell signalling defects. Br. J. Cancer 92, 305–311.

    PubMed  CAS  Google Scholar 

  6. Liu, C., Yu, S., Zinn, K. Wang, J., Zhang, L., Jia, Y., Kappes, J. C., Barnes, S., Kimberly, R. P., Grizzle, W. E., and Zhang, H. G. (2006) Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function J. Immunol. 176, 1375–1385.

    PubMed  CAS  Google Scholar 

  7. Frangsmyr, L., Baranov, V., Nagaeva, O., Stendahl, U., Kjellberg, L., and Mincheva-Nilsson, L., (2005) Cytoplasmic microvesicular form of Fas ligand in human early placenta: switching the tissue immune privilege hypothesis from cellular to vesicular level. Mol. Hum. Reprod. 11, 35–41.

    Article  PubMed  CAS  Google Scholar 

  8. Janowska-Wieczorek, A., Marquez-Curtis, L. A., Wysoczynski, M., and Ratajczak, M. Z. (2006) Enhancing effect of platelet-derived microvesicles on the invasive potential of breast cancer cells. Transfusion, 46, 1199–1209.

    Article  PubMed  Google Scholar 

  9. Janowska-Wieczorek, A., Wysoczynski, M., Kijowski, J., Marquez-Curtis, L., Machalinski, B., Ratajczak, J. and Ratajczak, M. Z. (2005) Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int. J. Cancer, 113, 752–760.

    Article  PubMed  CAS  Google Scholar 

  10. Whiteside, T. L. (2005) Tumour-derived exosomes or microvesicles: another mechanism of tumour escape from the host immune system? Br. J. Cancer 92, 209–211.

    Article  PubMed  CAS  Google Scholar 

  11. Delcayre, A. and Le Pecq, J. B. (2006) Exosomes as novel therapeutic nanodevices. Curr. Opin. Mol. Ther. 8, 31–38.

    PubMed  CAS  Google Scholar 

  12. Delcayre, A., Estelles, A., Sperinde, J., Roulon, T., Paz, P., Aguilar, B., Villanueva, J., Khine, S. and Le Pecq, J. B. (2005) Exosome display technology: applications to the development of new diagnostics and therapeutics. Blood Cells Mol. Dis., 35, 158–168.

    Article  PubMed  CAS  Google Scholar 

  13. Delcayre, A., Shu, H. and Le Pecq J. B. (2005) Dendritic cell-derived exosomes in cancer immunotherapy: exploiting nature’s antigen delivery pathway. Expert Rev. Anticancer Ther. 5, 537–547.

    Article  PubMed  CAS  Google Scholar 

  14. Thery, C., Zitvogel, L. and Amigorena, S. (2002) Exosomes: composition, biogenesis and function. Nat. Rev. Immunol., 2, 569–579.

    PubMed  CAS  Google Scholar 

  15. van Niel, G. and Heyman, M. (2002) The epithelial cell cytoskeleton and intracellular trafficking. II. Intestinal epithelial cell exosomes: perspectives on their structure and function. Am. J. Physiol. Gastrointest. Liver Physiol. 283, G251–255.

    PubMed  Google Scholar 

  16. Wubbolts, R. W., Leckie, R. S., Veenhuizen, P. T., Schwartzmann, G., Moebius, W., Hoernschemeyer, J., Slot, J. W., Geuze, H. J. and Stoorvogel, W. (2003) Proteomic and biochemical analyses of human B cell-derived exosomes: potential implications for their function and multivesicular body formation. J. Biol. Chem., 7, 7.

    Google Scholar 

  17. Denzer, K., van Eijk, M., Kleijmeer, M. J. Jakobson, E., de Groot C., and Geuze, H. J. (2000) Follicular dendritic cells carry MHC class II-expressing microvesicles at their surface. J. Immunol., 165, 1259–1265.

    PubMed  CAS  Google Scholar 

  18. Thery, C., Regnault, A., Garin, J., Wolfers, J., Zitvogel, L., Ricciardi-Castagnoli, P., Raposo, G. and Amigorena, S. (1999) Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. J. Cell. Biol. 147, 599–610.

    Article  PubMed  CAS  Google Scholar 

  19. Zitvogel, L., Regnault, A., Lozier, A., Wolfers, J., Flament, C., Tenza, D., Ricciardi-Castagnoli, P., Raposo, G. and Amigorena, S. (1998) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat. Med., 4, 594–600.

    Article  PubMed  CAS  Google Scholar 

  20. Mignot, G., Roux, S., Thery, C., Segura, E. and Zitvogel, L. (2006) Prospects for exosomes in, immunotherapy of cancer. J. Cell. Mol. Med., 10, 376–388.

    Article  PubMed  CAS  Google Scholar 

  21. Escudier, B., Dorval, T., Chaput, N., Andre, F., Caby, M. P., Novault, S., Flament, C., Leboulaire, C., Borg, C., Amigorena, S., Boccaccio, C., Bonnerot, C., Dhellin, O., Movassagh, M., Piperno, S., Robert, C., Serra, V., Valente, N., Le Pecq, J. B., Spatz, A., Lantz, O., Tursz, T., Angevin, E. and Zitvogel, L. (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.

    Article  PubMed  CAS  Google Scholar 

  22. Morse, M. A., Garst, J., Osada, T., Khan, S., Hobeika, A., Clay, T. M., Valente, N., Shreeniwas, R., Sutton, M. A., Delcayre, A., Hsu, D. H., Le Pecq, J. B. and Lyerly, H. K. (2005) A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J. Transl. Med. 3, 9.

    Article  PubMed  CAS  Google Scholar 

  23. Andre, F., Schartz, N. E., Movassagh, M., Flament, C., Pautier, P., Morice, P., Pomel, C., Lhomme, C., Escudier, B., Le Chevalier, T., Tursz, T., Amigorena, S., Raposo, G., Angevin, E. and Zitvogel, L. (2002) Malignant effusions and immunogenic tumour-derived exosomes. Lancet 360, 295–305.

    Article  PubMed  CAS  Google Scholar 

  24. Wolfers, J., Lozier, A., Raposo, G., Regnault, A., Thery, C., Masurier, C., Flament, C., Pouzieux, S., Faure, F., Tursz, T., Angevin, E., Amigorena, S., and Zitvogel, L. (2001) Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat. Med. 7, 297–303.

    Article  PubMed  CAS  Google Scholar 

  25. Hegmans, J. P., Bard, M. P., Hemmes, A., Luider, T. M., Kleijmeer M. J., Prins, J. B., Zitvogel, L., Burgers, S. A., Hoogsteden, H. C. and Lambrecht, B. N. (2004) Proteomic analysis of exosomes secreted by human mesothelioma cells. Am. J. Pathol., 164, 1807–1815.

    PubMed  CAS  Google Scholar 

  26. Rajagopalan, S., Olin, J. W., Young, S., Erikson, M., Grossman, P. M., Mendelsohn, F. O., Regensteiner, J. G., Hiatt, W. R. and Annex, B. H. (2004) Design of the Del-1 for therapeutic angiogenesis trial (DELTA-1), a phase II multicenter, double-blind placebo-controlled trial of VLTS-589 in subjects with intermittent claudication secondary to peripheral arterial disease. Hum. Gene Ther. 15, 619–624.

    Article  PubMed  CAS  Google Scholar 

  27. Zhong, J., Eliceiri, B., Stupack, D., Penta, K., Sakamoto, G., Quertermous, T., Coleman, M., Boudreau, N. and Varner, J. A. (2003) Neovascularization of ischemic tissues by gene delivery of the extracellular matrix protein Del-1. J. Clin. Invest. 112, 30–41.

    PubMed  CAS  Google Scholar 

  28. Hegmans, J. P., Hemmes, A., Aerts, J. G., Hoogsteden, H. C. and Lambrecht, B. N. (2005) Immunotherapy of murine malignant mesothelioma using tumor lysatepulsed dendritic cells. Am. J. Respir. Crit. Care Med. 171, 1168–1177.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Humana Press, Totowa, NJ

About this protocol

Cite this protocol

Hegmans, J.P.J.J., Gerber, P.J., Lambrecht, B.N. (2008). Exosomes. In: Thompson, J.D., Ueffing, M., Schaeffer-Reiss, C. (eds) Functional Proteomics. Methods in Molecular Biology, vol 484. Humana Press. https://doi.org/10.1007/978-1-59745-398-1_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-398-1_7

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-971-0

  • Online ISBN: 978-1-59745-398-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics