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Clinical and Developmental Immunology
Volume 2011, Article ID 842849, 11 pages
http://dx.doi.org/10.1155/2011/842849
Review Article

The Roles of Tumor-Derived Exosomes in Cancer Pathogenesis

Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA

Received 9 July 2011; Accepted 28 August 2011

Academic Editor: Hisae Iinuma

Copyright © 2011 Chenjie Yang and Paul D. Robbins. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. E. G. Trams, C. J. Lauter, Norman Salem, and U. Heine, “Exfoliation of membrane ecto-enzymes in the form of micro-vesicles,” Biochim Biophys Acta, vol. 645, no. 1, pp. 63–70, 1981. View at Google Scholar · View at Scopus
  2. B. T. Pan, K. Teng, and C. Wu, “Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes,” Journal of Cell Biology, vol. 101, no. 3, pp. 942–948, 1985. View at Google Scholar · View at Scopus
  3. R. M. Johnstone, M. Adam, J. R. Hammond, L. Orr, and C. Turbide, “Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes),” Journal of Biological Chemistry, vol. 262, no. 19, pp. 9412–9420, 1987. View at Google Scholar · View at Scopus
  4. R. M. Johnstone, A. Bianchini, and K. Teng, “Reticulocyte maturation and exosome release: transferrin receptor containing exosomes shows multiple plasma membrane functions,” Blood, vol. 74, no. 5, pp. 1844–1851, 1989. View at Google Scholar · View at Scopus
  5. C. Théry, M. Ostrowski, and E. Segura, “Membrane vesicles as conveyors of immune responses,” Nature Reviews Immunology, vol. 9, no. 8, pp. 581–593, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. K. Denzer, M. J. Kleijmeer, H. F. G. Heijnen, W. Stoorvogel, and H. J. Geuze, “Exosome: from internal vesicle of the multivesicular body to intercellular signaling device,” Journal of Cell Science, vol. 113, no. 19, pp. 3365–3374, 2000. View at Google Scholar · View at Scopus
  7. W. Stoorvogel, M. J. Kleijmeer, H. J. Geuze, and G. Raposo, “The biogenesis and functions of exosomes,” Traffic, vol. 3, no. 5, pp. 321–330, 2002. View at Publisher · View at Google Scholar · View at Scopus
  8. C. Théry, L. Zitvogel, and S. Amigorena, “Exosomes: composition, biogenesis and function,” Nature Reviews Immunology, vol. 2, no. 8, pp. 569–579, 2002. View at Google Scholar · View at Scopus
  9. C. Géminard, A. De Gassart, and M. Vidal, “Reticulocyte maturation: mitoptosis and exosome release,” Biocell, vol. 26, no. 2, pp. 205–215, 2002. View at Google Scholar · View at Scopus
  10. C. M. Fader, A. Savina, D. Sánchez, and M. I. Colombo, “Exosome secretion and red cell maturation: exploring molecular components involved in the docking and fusion of multivesicular bodies in K562 cells,” Blood Cells, Molecules, and Diseases, vol. 35, no. 2, pp. 153–157, 2005. View at Publisher · View at Google Scholar · View at Scopus
  11. L. Zitvogel, A. Regnault, A. Lozier et al., “Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes,” Nature Medicine, vol. 4, no. 5, pp. 594–600, 1998. View at Publisher · View at Google Scholar · View at Scopus
  12. G. Raposo, H. W. Nijman, W. Stoorvogel et al., “B lymphocytes secrete antigen-presenting vesicles,” Journal of Experimental Medicine, vol. 183, no. 3, pp. 1161–1172, 1996. View at Publisher · View at Google Scholar · View at Scopus
  13. A. Clayton, A. Turkes, H. Navabi, M. D. Mason, and Z. Tabi, “Induction of heat shock proteins in B-cell exosomes,” Journal of Cell Science, vol. 118, no. 16, pp. 3631–3638, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. P. J. Peters, H. J. Geuze, H. A. Van Der Donk et al., “Molecules relevant for T cell-target cell interaction are present in cytolytic granules of human T lymphocytes,” European Journal of Immunology, vol. 19, no. 8, pp. 1469–1475, 1989. View at Google Scholar · View at Scopus
  15. N. Blanchard, D. Lankar, F. Faure et al., “TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/ζ complex,” Journal of Immunology, vol. 168, no. 7, pp. 3235–3241, 2002. View at Google Scholar · View at Scopus
  16. H. F. G. Heijnen, A. E. Schiel, R. Fijnheer, H. J. Geuze, and J. J. Sixma, “Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and α-granules,” Blood, vol. 94, no. 11, pp. 3791–3799, 1999. View at Google Scholar · View at Scopus
  17. D. Skokos, H. G. Botros, C. Demeure et al., “Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responses in vivo,” Journal of Immunology, vol. 170, no. 6, pp. 3037–3045, 2003. View at Google Scholar · View at Scopus
  18. G. Raposo, D. Tenza, S. Mecheri, R. Peronet, C. Bonnerot, and C. Desaymard, “Accumulation of major histocompatibility complex class II molecules in mast cell secretory granules and their release upon degranulation,” Molecular Biology of the Cell, vol. 8, no. 12, pp. 2631–2645, 1997. View at Google Scholar · View at Scopus
  19. S. Bhatnagar, K. Shinagawa, F. J. Castellino, and J. S. Schorey, “Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo,” Blood, vol. 110, no. 9, pp. 3234–3244, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. G. van Niel, G. Raposo, C. Candalh et al., “Intestinal epithelial cells secrete exosome-like vesicles,” Gastroenterology, vol. 121, no. 2, pp. 337–349, 2001. View at Google Scholar · View at Scopus
  21. A. Lespagnol, D. Duflaut, C. Beekman et al., “Exosome secretion, including the DNA damage-induced p53-dependent secretory pathway, is severely compromised in TSAP6/Steap3-null mice,” Cell Death and Differentiation, vol. 15, no. 11, pp. 1723–1733, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. J. Fauré, G. Lachenal, M. Court et al., “Exosomes are released by cultured cortical neurones,” Molecular and Cellular Neuroscience, vol. 31, no. 4, pp. 642–648, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. X. Yu, S. L. Harris, and A. J. Levine, “The regulation of exosome secretion: a novel function of the p53 protein,” Cancer Research, vol. 66, no. 9, pp. 4795–4801, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. H. Matsuo, J. Chevallier, N. Mayran et al., “Role of LBPA and Alix in Multivesicular Liposome Formation and Endosome Organization,” Science, vol. 303, no. 5657, pp. 531–534, 2004. View at Publisher · View at Google Scholar · View at Scopus
  25. G. Mignot, S. Roux, C. Thery, E. Ségura, and L. Zitvogel, “Prospects for exosomes in immunotherapy of cancer,” Journal of Cellular and Molecular Medicine, vol. 10, no. 2, pp. 376–388, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Clayton and M. D. Mason, “Exosomes in tumour immunity,” Current Oncology, vol. 16, no. 3, pp. 46–49, 2009. View at Google Scholar · View at Scopus
  27. H. Valadi, K. Ekström, A. Bossios, M. Sjöstrand, J. J. Lee, and J. O. Lötvall, “Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells,” Nature Cell Biology, vol. 9, no. 6, pp. 654–659, 2007. View at Publisher · View at Google Scholar
  28. J. Skog, T. Würdinger, S. van Rijn et al., “Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers,” Nature Cell Biology, vol. 10, no. 12, pp. 1470–1476, 2008. View at Publisher · View at Google Scholar · View at Scopus
  29. D. D. Taylor and C. Gercel-Taylor, “MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer,” Gynecologic Oncology, vol. 110, no. 1, pp. 13–21, 2008. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Ratajczak, M. Wysoczynski, F. Hayek, A. Janowska-Wieczorek, and M. Z. Ratajczak, “Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication,” Leukemia, vol. 20, no. 9, pp. 1487–1495, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. F. Coutant, L. Perrin-Cocon, S. Agaugué, T. Delair, P. André, and V. Lotteau, “Mature dendritic cell generation promoted by lysophosphatidylcholine,” Journal of Immunology, vol. 169, no. 4, pp. 1688–1695, 2002. View at Google Scholar
  32. F. Andre, N. E. C. Schartz, M. Movassagh et al., “Malignant effusions and immunogenic tumour-derived exosomes,” Lancet, vol. 360, no. 9329, pp. 295–305, 2002. View at Publisher · View at Google Scholar · View at Scopus
  33. J. Wolfers, A. Lozier, G. Raposo et al., “Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming,” Nature Medicine, vol. 7, no. 3, pp. 297–303, 2001. View at Publisher · View at Google Scholar · View at Scopus
  34. S. Dai, T. Wan, B. Wang et al., “More efficient induction of HLA-A*0201-restricted and carcinoembryonic antigen (CEA) - Specific CTL response by immunization with exosomes prepared from heat-stressed CEA-positive tumor cells,” Clinical Cancer Research, vol. 11, no. 20, pp. 7554–7563, 2005. View at Publisher · View at Google Scholar · View at Scopus
  35. A. Clayton, J. P. Mitchell, J. Court, M. D. Mason, and Z. Tabi, “Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2,” Cancer Research, vol. 67, no. 15, pp. 7458–7466, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. N. Bu, H. Wu, B. Sun et al., “Exosome-loaded dendritic cells elicit tumor-specific CD8(+) cytotoxic T cells in patients with glioma,” Journal of Neuro-Oncology, vol. 104, no. 3, pp. 659–667. View at Publisher · View at Google Scholar
  37. S. Dai, X. Zhou, B. Wang et al., “Enhanced induction of dendritic cell maturation and HLA-A*0201-restricted CEA-specific CD8(+) CTL response by exosomes derived from IL-18 gene-modified CEA-positive tumor cells,” Journal of Molecular Medicine, vol. 84, no. 12, pp. 1067–1076, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. Y. Zhang, C. L. I. Luo, B. C. He, J. M. Zhang, G. Cheng, and X. H. Wu, “Exosomes derived from IL-12-anchored renal cancer cells increase induction of specific antitumor response in vitro: a novel vaccine for renal cell carcinoma,” International Journal of Oncology, vol. 36, no. 1, pp. 133–140, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. Yang, F. Xiu, Z. Cai et al., “Increased induction of antitumor response by exosomes derived from interleukin-2 gene-modified tumor cells,” Journal of Cancer Research and Clinical Oncology, vol. 133, no. 6, pp. 389–399, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. W. Chen, J. Wang, C. Shao et al., “Efficient induction of antitumor T cell immunity by exosomes derived from heat-shocked lymphoma cells,” European Journal of Immunology, vol. 36, no. 6, pp. 1598–1607, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. J. A. Cho, Y. S. Lee, S. H. Kim, J. K. Ko, and C. W. Kim, “MHC independent anti-tumor immune responses induced by Hsp70-enriched exosomes generate tumor regression in murine models,” Cancer Letters, vol. 275, no. 2, pp. 256–265, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. Y. Xie, O. Bai, H. Zhang et al., “Membrane-bound HSP70-engineered myeloma cell-derived exosomes stimulate more efficient CD8+ CTL- and NK-mediated antitumour immunity than exosomes released from heat-shocked tumour cells expressing cytoplasmic HSP70,” Journal of Cellular and Molecular Medicine, vol. 14, no. 11, pp. 2655–2666, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. T. Chen, J. Guo, M. Yang, X. Zhu, and X. Cao, “Chemokine-containing exosomes are released from heat-stressed tumor cells via lipid raft-dependent pathway and act as efficient tumor vaccine,” Journal of Immunology, vol. 186, no. 4, pp. 2219–2228, 2011. View at Publisher · View at Google Scholar
  44. F. Xiu, Z. Cai, Y. Yang, X. Wang, J. Wang, and X. Cao, “Surface anchorage of superantigen SEA promotes induction of specific antitumor immune response by tumor-derived exosomes,” Journal of Molecular Medicine, vol. 85, no. 5, pp. 511–521, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. I. S. Zeelenberg, M. Ostrowski, S. Krumeich et al., “Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses,” Cancer Research, vol. 68, no. 4, pp. 1228–1235, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. H. Navabi, D. Croston, J. Hobot et al., “Preparation of human ovarian cancer ascites-derived exosomes for a clinical trial,” Blood Cells, Molecules, and Diseases, vol. 35, no. 2, pp. 149–152, 2005. View at Publisher · View at Google Scholar · View at Scopus
  47. S. Dai, D. Wei, Z. Wu et al., “Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer,” Molecular Therapy, vol. 16, no. 4, pp. 782–790, 2008. View at Publisher · View at Google Scholar · View at Scopus
  48. E. Ristorcelli, E. Beraud, P. Verrando et al., “Human tumor nanoparticles induce apoptosis of pancreatic cancer cells,” FASEB Journal, vol. 22, no. 9, pp. 3358–3369, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. E. Ristorcelli, E. Beraud, S. Mathieu, D. Lombardo, and A. Verine, “Essential role of Notch signaling in apoptosis of human pancreatic tumoral cells mediated by exosomal nanoparticles,” International Journal of Cancer, vol. 125, no. 5, pp. 1016–1026, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. D. D. Poutsiaka, E. W. Schroder, and D. D. Taylor, “Membrane vesicles shed by murine melanoma cells selectively inhibit the expression of Ia antigen by macrophages,” Journal of Immunology, vol. 134, no. 1, pp. 138–144, 1985. View at Google Scholar · View at Scopus
  51. G. Andreola, L. Rivoltini, C. Castelli et al., “Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles,” Journal of Experimental Medicine, vol. 195, no. 10, pp. 1303–1316, 2002. View at Publisher · View at Google Scholar · View at Scopus
  52. V. Huber, S. Fais, M. Iero et al., “Human colorectal cancer cells induce T-cell death through release of proapoptotic microvesicles: role in immune escape,” Gastroenterology, vol. 128, no. 7, pp. 1796–1804, 2005. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Klibi, T. Niki, A. Riedel et al., “Blood diffusion and Th1-suppressive effects of galectin-9-containing exosomes released by Epstein-Barr virus-infected nasopharyngeal carcinoma cells,” Blood, vol. 113, no. 9, pp. 1957–1966, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. D. D. Taylor, C. Gercel-Taylor, K. S. Lyons, J. Stanson, and T. L. Whiteside, “T-Cell apoptosis and suppression of T-Cell receptor/CD3-ζ by fas ligand-containing membrane vesicles shed from ovarian tumors,” Clinical Cancer Research, vol. 9, no. 14, pp. 5113–5119, 2003. View at Google Scholar · View at Scopus
  55. A. Clayton and Z. Tabi, “Exosomes and the MICA-NKG2D system in cancer,” Blood Cells, Molecules, and Diseases, vol. 34, no. 3, pp. 206–213, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. A. Clayton, J. P. Mitchell, J. Court, S. Linnane, M. D. Mason, and Z. Tabi, “Human tumor-derived exosomes down-modulate NKG2D expression,” Journal of Immunology, vol. 180, no. 11, pp. 7249–7258, 2008. View at Google Scholar · View at Scopus
  57. C. Liu, S. Yu, K. Zinn et al., “Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function,” Journal of Immunology, vol. 176, no. 3, pp. 1375–1385, 2006. View at Google Scholar · View at Scopus
  58. R. Valenti, V. Huber, P. Filipazzi et al., “Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-β-mediated suppressive activity on T lymphocytes,” Cancer Research, vol. 66, no. 18, pp. 9290–9298, 2006. View at Publisher · View at Google Scholar · View at Scopus
  59. S. Yu, C. Liu, K. Su et al., “Tumor exosomes inhibit differentiation of bone marrow dendritic cells,” Journal of Immunology, vol. 178, no. 11, pp. 6867–6875, 2007. View at Google Scholar · View at Scopus
  60. X. Xiang, A. Poliakov, C. Liu et al., “Induction of myeloid-derived suppressor cells by tumor exosomes,” International Journal of Cancer, vol. 124, no. 11, pp. 2621–2633, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. Y. Liu, X. Xiang, X. Zhuang et al., “Contribution of MyD88 to the tumor exosome-mediated induction of myeloid derived suppressor cells,” American Journal of Pathology, vol. 176, no. 5, pp. 2490–2499, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. F. Chalmin, S. Ladoire, G. Mignot et al., “Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells,” Journal of Clinical Investigation, vol. 120, no. 2, pp. 457–471, 2010. View at Publisher · View at Google Scholar · View at Scopus
  63. X. Xiang, Y. Liu, X. Zhuang et al., “TLR2-mediated expansion of MDSCs is dependent on the source of tumor exosomes,” American Journal of Pathology, vol. 177, no. 4, pp. 1606–1610, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. G. Mignot, F. Chalmin, S. Ladoire, C. Rébé, and F. Ghiringhelli, “Tumor exosome-mediated MDSC activation,” American Journal of Pathology, vol. 178, no. 3, pp. 1403–1404, 2011. View at Publisher · View at Google Scholar
  65. H. Peinado, S. Lavotshkin, and D. Lyden, “The secreted factors responsible for pre-metastatic niche formation: old sayings and new thoughts,” Seminars in Cancer Biology, vol. 21, no. 2, pp. 139–146, 2011. View at Publisher · View at Google Scholar
  66. J. M. Aliotta, M. Pereira, K. W. Johnson et al., “Microvesicle entry into marrow cells mediates tissue-specific changes in mRNA by direct delivery of mRNA and induction of transcription,” Experimental Hematology, vol. 38, no. 3, pp. 233–245, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. J. Ratajczak, K. Miekus, M. Kucia et al., “Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery,” Leukemia, vol. 20, no. 5, pp. 847–856, 2006. View at Publisher · View at Google Scholar · View at Scopus
  68. M. Szajnik, M. Czystowska, M. J. Szczepanski, M. Mandapathil, and T. L. Whiteside, “Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T cells (Treg),” PLoS ONE, vol. 5, no. 7, Article ID e11469, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. J. Wada, H. Onishi, H. Suzuki et al., “Surface-bound TGF-β1 on effusion-derived exosomes participates in maintenance of number and suppressive function of regulatory T-cells in malignant effusions,” Anticancer Research, vol. 30, no. 9, pp. 3747–3757, 2010. View at Google Scholar · View at Scopus
  70. C. Yang, S. H. Kim, N. R. Bianco, and P. D. Robbins, “Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model,” PLoS ONE, vol. 6, no. 8, article e22517, 2011. View at Publisher · View at Google Scholar
  71. J. P. J. J. Hegmans, M. P. L. Bard, A. Hemmes et al., “Proteomic Analysis of Exosomes Secreted by Human Mesothelioma Cells,” American Journal of Pathology, vol. 164, no. 5, pp. 1807–1815, 2004. View at Google Scholar · View at Scopus
  72. J. L. Hood, H. Pan, G. M. Lanza, and S. A. Wickline, “Paracrine induction of endothelium by tumor exosomes,” Laboratory Investigation, vol. 89, no. 11, pp. 1317–1328, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. J. L. Hood, R. S. San, and S. A. Wickline, “Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis,” Cancer Research, vol. 71, no. 11, pp. 3792–3801, 2011. View at Publisher · View at Google Scholar
  74. S. Gesierich, I. Berezovskiy, E. Ryschich, and M. Zöller, “Systemic induction of the angiogenesis switch by the tetraspanin D6.1A/CO-029,” Cancer Research, vol. 66, no. 14, pp. 7083–7094, 2006. View at Publisher · View at Google Scholar · View at Scopus
  75. I. Nazarenko, S. Rana, A. Baumann et al., “Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation,” Cancer Research, vol. 70, no. 4, pp. 1668–1678, 2010. View at Publisher · View at Google Scholar · View at Scopus
  76. H. Sheldon, E. Heikamp, H. Turley et al., “New mechanism for Notch signaling to endothelium at a distance by delta-like 4 incorporation into exosomes,” Blood, vol. 116, no. 13, pp. 2385–2394, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. J. Webber, R. Steadman, M. D. Mason, Z. Tabi, and A. Clayton, “Cancer exosomes trigger fibroblast to myofibroblast differentiation,” Cancer Research, vol. 70, no. 23, pp. 9621–9630, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. R. Nieuwland, J. A.M. Van Der Post, C. A.R. Lok Gemma, G. Kenter, and A. Sturk, “Microparticles and exosomes in gynecologic neoplasias,” Seminars in Thrombosis and Hemostasis, vol. 36, no. 8, pp. 925–929, 2010. View at Publisher · View at Google Scholar
  79. S. Runz, S. Keller, C. Rupp et al., “Malignant ascites-derived exosomes of ovarian carcinoma patients contain CD24 and EpCAM,” Gynecologic Oncology, vol. 107, no. 3, pp. 563–571, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. A. Stoeck, S. Keller, S. Riedle et al., “A role for exosomes in the constitutive and stimulus-induced ectodomain cleavage of L1 and CD44,” Biochemical Journal, vol. 393, no. 3, pp. 609–618, 2006. View at Publisher · View at Google Scholar · View at Scopus
  81. T. Jung, D. Castellana, P. Klingbeil et al., “CD44v6 dependence of premetastatic niche preparation by exosomes,” Neoplasia, vol. 11, no. 10, pp. 1093–1105, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. M. Wysoczynski and M. Z. Ratajczak, “Lung cancer secreted microvesicles: underappreciated modulators of microenvironment in expanding tumors,” International Journal of Cancer, vol. 125, no. 7, pp. 1595–1603, 2009. View at Publisher · View at Google Scholar · View at Scopus
  83. C. Grange, M. Tapparo, F. Collino et al., “Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche,” Cancer Research, vol. 71, no. 15, pp. 5346–5356, 2011. View at Publisher · View at Google Scholar
  84. D. Castellana, F. Zobairi, M. C. Martinez et al., “Membrane microvesicles as actors in the establishment of a favorable prostatic tumoral niche: a role for activated fibroblasts and CX3CL1-CX3CR1 axis,” Cancer Research, vol. 69, no. 3, pp. 785–793, 2009. View at Publisher · View at Google Scholar · View at Scopus
  85. L. E. Graves, E. V. Ariztia, J. R. Navari, H. J. Matzel, M. S. Stack, and D. A. Fishman, “Proinvasive properties of ovarian cancer ascites-derived membrane vesicles,” Cancer Research, vol. 64, no. 19, pp. 7045–7049, 2004. View at Publisher · View at Google Scholar · View at Scopus
  86. V. Dolo, S. D'Ascenzo, S. Violini et al., “Matrix-degrading proteinases are shed in membrane vesicles by ovarian cancer cells in vivo and in vitro,” Clinical and Experimental Metastasis, vol. 17, no. 2, pp. 131–140, 1999. View at Publisher · View at Google Scholar · View at Scopus
  87. V. Dolo, A. Ginestra, G. Ghersi, H. Nagase, and M. L. Vittorelli, “Human breast carcinoma cells cultured in the presence of serum shed membrane vesicles rich in gelatinolytic activities,” Journal of Submicroscopic Cytology and Pathology, vol. 26, no. 2, pp. 173–180, 1994. View at Google Scholar · View at Scopus
  88. J. Rak, “Microparticles in cancer,” Seminars in Thrombosis and Hemostasis, vol. 36, no. 8, pp. 888–906, 2010. View at Publisher · View at Google Scholar
  89. H. F. Dvorak, S. C. Quay, and N. S. Orenstein, “Tumor shedding and coagulation,” Science, vol. 212, no. 4497, pp. 923–924, 1981. View at Google Scholar · View at Scopus
  90. H. F. Dvorak, L. van de Water, and A. M. Bitzer, “Procoagulant activity associated with plasma membrane vesicles shed by cultured tumor cells,” Cancer Research, vol. 43, no. 9, pp. 4434–4442, 1983. View at Google Scholar
  91. M. E. T. Tesselaar, F. P. H. T. M. Romijn, I. K. Van Der Linden, F. A. Prins, R. M. Bertina, and S. Osanto, “Microparticle-associated tissue factor activity: a link between cancer and thrombosis?” Journal of Thrombosis and Haemostasis, vol. 5, no. 3, pp. 520–527, 2007. View at Publisher · View at Google Scholar · View at Scopus
  92. N. Yokota, S. Koizume, E. Miyagi et al., “Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells,” British Journal of Cancer, vol. 101, no. 12, pp. 2023–2029, 2009. View at Publisher · View at Google Scholar · View at Scopus
  93. A. Zomer, T. Vendrig, E. S. Hopmans, M. van Eijndhoven, J. M. Middeldorp, and D. M. Pegtel, “Exosomes: fit to deliver small RNA,” Communicative & Integrative Biology, vol. 3, pp. 447–450, 2010. View at Google Scholar
  94. K. Ohshima, K. Inoue, A. Fujiwara et al., “Let-7 microRNA family Is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line,” PLoS ONE, vol. 5, no. 10, Article ID e13247, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. D. G. Meckes, K. H. Y. Shair, A. R. Marquitz, C. P. Kung, R. H. Edwards, and N. Raab-Traub, “Human tumor virus utilizes exosomes for intercellular communication,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 47, pp. 20370–20375, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. C. Gourzones, A. Gelin, I. Bombik et al., “Extra-cellular release and blood diffusion of BART viral micro-RNAs produced by EBV-infected nasopharyngeal carcinoma cells,” Virology Journal, vol. 7, p. 271, 2010. View at Publisher · View at Google Scholar
  97. S. Khan, J. R. Aspe, M. G. Asumen et al., “Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential,” British Journal of Cancer, vol. 100, no. 7, pp. 1073–1086, 2009. View at Publisher · View at Google Scholar · View at Scopus
  98. S. Khan, J. M. S. Jutzy, J. R. Aspe, D. W. McGregor, J. W. Neidigh, and N. R. Wall, “Survivin is released from cancer cells via exosomes,” Apoptosis, pp. 1–12, 2011. View at Publisher · View at Google Scholar · View at Scopus
  99. R. Safaei, B. J. Larson, T. C. Cheng et al., “Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells,” Molecular Cancer Therapeutics, vol. 4, no. 10, pp. 1595–1604, 2005. View at Publisher · View at Google Scholar · View at Scopus
  100. K. G. Chen, J. C. Valencia, B. Lai et al., “Melanosomal sequestration of cytotoxic drugs contributes to the intractability of malignant melanomas,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 26, pp. 9903–9907, 2006. View at Publisher · View at Google Scholar · View at Scopus
  101. F. Luciani, M. Spada, A. De Milito et al., “Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs,” Journal of the National Cancer Institute, vol. 96, no. 22, pp. 1702–1713, 2004. View at Publisher · View at Google Scholar · View at Scopus
  102. V. Ciravolo, V. Huber, G. C. Ghedini et al., “Potential role of HER2-overexpressing exosomes in counteringTrastuzumab-based therapy,” Journal of Cellular Physiology. In press. View at Publisher · View at Google Scholar
  103. C. Battke, R. Ruiss, U. Welsch et al., “Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC,” Cancer Immunology, Immunotherapy, vol. 60, no. 5, pp. 639–648, 2011. View at Publisher · View at Google Scholar
  104. M. Iero, R. Valenti, V. Huber et al., “Tumour-released exosomes and their implications in cancer immunity,” Cell Death and Differentiation, vol. 15, no. 1, pp. 80–88, 2008. View at Publisher · View at Google Scholar · View at Scopus
  105. B. Toth, R. Nieuwland, S. Liebhardt et al., “Circulating microparticles in breast cancer patients: a comparative analysis with established biomarkers,” Anticancer Research, vol. 28, no. 2 A, pp. 1107–1112, 2008. View at Google Scholar · View at Scopus
  106. W. K. Jeong, E. Wieckowski, D. D. Taylor, T. E. Reichert, S. Watkins, and T. L. Whiteside, “Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes,” Clinical Cancer Research, vol. 11, no. 3, pp. 1010–1020, 2005. View at Google Scholar · View at Scopus
  107. T. E. Ichim, Z. Zhong, S. Kaushal et al., “Exosomes as a tumor immune escape mechanism: possible therapeutic implications,” Journal of Translational Medicine, vol. 6, article no. 37, 2008. View at Publisher · View at Google Scholar · View at Scopus
  108. R. H. Tullis, J. A. Ambrus, and J. A. Joyce, “HIV affinity hemodialysis as a treatment for AIDS,” American Clinical Laboratory, vol. 20, no. 9, pp. 22–23, 2001. View at Google Scholar · View at Scopus
  109. R. H. Tullis, R. P. Duffin, M. Zech, and J. L. Ambrus, “Affinity hemodialysis for antiviral therapy. I. Removal of HIV-1 from cell culture supernatants, plasma, and blood,” Therapeutic Apheresis, vol. 6, no. 3, pp. 213–220, 2002. View at Publisher · View at Google Scholar · View at Scopus
  110. R. H. Tullis, R. P. Duffin, M. Zech, and J. L. Ambrus, “Affinity hemodialysis for antiviral therapy. II. Removal of HIV-1 viral proteins from cell culture supernatants and whole blood,” Blood Purification, vol. 21, no. 1, pp. 58–63, 2003. View at Publisher · View at Google Scholar · View at Scopus
  111. J. Li, C. A. Sherman-Baust, M. Tsai-Turton, R. E. Bristow, R. B. Roden, and P. J. Morin, “Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer,” BMC cancer, vol. 9, p. 244, 2009. View at Google Scholar · View at Scopus
  112. S. Keller, A. -K. König, F. Marmé et al., “Systemic presence and tumor-growth promoting effect of ovarian carcinoma released exosomes,” Cancer Letters, vol. 278, no. 1, pp. 73–81, 2009. View at Publisher · View at Google Scholar