The genomic and proteomic content of cancer cell-derived exosomes

Frontiers in Oncology

Volumn 2, Issue APR, 2012, Pages

  Henderson, Meredith C ^a   Azorsa, David O ^a  

^a TRANSLATIONAL GENOMICS RESEARCH INSTITUTE   (United States)

Author keywords

Cancer; Detection; Exosomes; Microvesicles

Indexed keywords

AMPHIREGULIN; CD44V6 ANTIGEN; CYCLIN DEPENDENT KINASE 8; EPIDERMAL GROWTH FACTOR RECEPTOR; HEAT SHOCK PROTEIN 90; LATENT MEMBRANE PROTEIN 1; MESSENGER RNA; MICRORNA; MICRORNA 21; MUCIN 1; PROTEIN; TRASTUZUMAB;

ANGIOGENESIS; BLADDER CANCER; BREAST CANCER; CANCER DIAGNOSIS; CARCINOGENICITY; CELL FUNCTION; CELL MIGRATION; DISEASE COURSE; DNA DAMAGE; EXOSOME; HUMAN; HYPOXIA; LUNG NON SMALL CELL CANCER; MASS SPECTROMETRY; NEOPLASM; POLYACRYLAMIDE GEL ELECTROPHORESIS; PROTEIN EXPRESSION; PROTEOMICS; REVIEW; TUMOR CELL;

EID: 84870586668     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2012.00038     Document Type: Review

References (88)

1. Adamczyk, K. A., Klein-Scory, S., Tehrani, M. M., Warnken, U., Schmiegel, W., Schnolzer, M., and Schwarte-Waldhoff, I. (2011). Characterization of soluble and exosomal forms of the EGFR released from pancreatic cancer cells. Life Sci. 89, 304-312.
2. Ahmed, F. E. (2007). Role of miRNA in carcinogenesis and biomarker selection: a methodological view. Expert Rev. Mol. Diagn. 7, 569-603.
3. Arroyo, J. D., Chevillet, J. R., Kroh, E. M., Ruf, I. K., Pritchard, C. C., Gibson, D. F., Mitchell, P. S., Bennett, C. F., Pogosova-Agadjanyan, E. L., Stirewalt, D. L., Tait, J. F., and Tewari, M. (2011). Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc. Natl. Acad. Sci. U.S.A. 108, 5003-5008.
4. Asangani, I. A., Rasheed, S. A., Nikolova, D. A., Leupold, J. H., Colburn, N. H., Post, S., and Allgayer, H. (2008). MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27, 2128-2136.
5. Bobrie, A., Colombo, M., Raposo, G., and Thery, C. (2011). Exosome secretion: molecular mechanisms and roles in immune responses. Traffic 12, 1659-1668.
6. Bu, N., Li, Q. L., Feng, Q., and Sun, B. Z. (2006). Immune protection effect of exosomes against attack of L1210 tumor cells. Leuk. Lymphoma 47, 913-918.
7. Chan, J. A., Krichevsky, A. M., and Kosik, K. S. (2005). MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 65, 6029-6033.
8. Chaput, N., and Thery, C. (2011). Exosomes: immune properties and potential clinical implementations. Semin. Immunopathol. 33, 419-440.
9. Chen, W., Wang, J., Shao, C., Liu, S., Yu, Y., Wang, Q., and Cao, X. (2006). Efficient induction of antitumor T cell immunity by exosomes derived from heat-shocked lymphoma cells. Eur. J. Immunol. 36, 1598-1607.
10. Clayton, A., and Tabi, Z. (2005). Exosomes and the MICA-NKG2D system in cancer. Blood Cells Mol. Dis. 34, 206-213.
11. Corcoran, C., Friel, A. M., Duffy, M. J., Crown, J., and O'Driscoll, L. (2011). Intracellular and extracellular microRNAs in breast cancer. Clin. Chem. 57, 18-32.
12. de Gassart, A., Geminard, C., Fevrier, B., Raposo, G., and Vidal, M. (2003). Lipid raft-associated protein sorting in exosomes. Blood 102, 4336-4344.
13. 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(Pt 19), 3365-3374.
14. Gesierich, S., Berezovskiy, I., Ryschich, E., and Zoller, M. (2006). Systemic induction of the angiogenesis switch by the tetraspanin D6.1A/CO-029. Cancer Res. 66, 7083-7094.
15. Gong, C., Yao, Y., Wang, Y., Liu, B., Wu, W., Chen, J., Su, F., Yao, H., and Song, E. (2011). Up-regulation of miR-21 mediates resistance to trastuzumab therapy for breast cancer. J. Biol. Chem. 286, 19127-19137.
16. Gonzales, P. A., Pisitkun, T., Hoffert, J. D., Tchapyjnikov, D., Star, R. A., Kleta, R., Wang, N. S., and Knepper, M. A. (2009). Large-scale proteomics and phosphoproteomics of urinary exosomes. J. Am. Soc. Nephrol. 20, 363-379.
17. Gonzales, P. A., Zhou, H., Pisitkun, T., Wang, N. S., Star, R. A., Knepper, M. A., and Yuen, P. S. (2010). Isolation and purification of exosomes in urine. Methods Mol. Biol. 641, 89-99.
18. Graner, M. W., Alzate, O., Dechkovskaia, A. M., Keene, J. D., Sampson, J. H., Mitchell, D. A., and Bigner, D. D. (2009). Proteomic and immunologic analyses of brain tumor exosomes. FASEB J. 23, 1541-1557.
19. Hanahan, D., and Weinberg, R. A. (2000). The hallmarks of cancer. Cell 100, 57-70.
20. 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.
21. Higginbotham, J. N., Demory Beckler, M., Gephart, J. D., Franklin, J. L., Bogatcheva, G., Kremers, G. J., Piston, D. W., Ayers, G. D., Mcconnell, R. E., Tyska, M. J., and Coffey, R. J. (2011). Amphiregulin exosomes increase cancer cell invasion. Curr. Biol. 21, 779-786.
22. Ho, H. K., Jang, J. J., Kaji, S., Spektor, G., Fong, A., Yang, P., Hu, B. S., Schatzman, R., Quertermous, T., and Cooke, J. P. (2004). Developmental endothelial locus-1 (Del-1), a novel angiogenic protein: its role in ischemia. Circulation 109, 1314-1319.
23. Hong, B. S., Cho, J. H., Kim, H., Choi, E. J., Rho, S., Kim, J., Kim, J. H., Choi, D. S., Kim, Y. K., Hwang, D., and Gho, Y. S. (2009). Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells. BMC Genomics 10, 556. doi:10.1186/1471-2164-10-556
24. Iorio, M. V., Ferracin, M., Liu, C. G., Veronese, A., Spizzo, R., Sabbioni, S., Magri, E., Pedriali, M., Fabbri, M., Campiglio, M., Menard, S., Palazzo, J. P., Rosenberg, A., Musiani, P., Volinia, S., Nenci, I., Calin, G. A., Querzoli, P., Negrini, M., and Croce, C. M. (2005). MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 65, 7065-7070.
25. Johnson, S. M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., Labourier, E., Reinert, K. L., Brown, D., and Slack, F. J. (2005). RAS is regulated by the let-7 microRNA family. Cell 120, 635-647.
26. Johnstone, R. M. (1992). The Jeanne Manery-Fisher Memorial Lecture 1991. Maturation of reticulocytes: formation of exosomes as a mechanism for shedding membrane proteins. Biochem. Cell Biol. 70, 179-190.
27. Johnstone, R. M. (2006). Exosomes biological significance: a concise review. Blood Cells Mol. Dis. 36, 315-321.
28. 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.
29. Johnstone, R. M., Bianchini, A., and Teng, K. (1989). Reticulocyte maturation and exosome release: transferrin receptor containing exosomes shows multiple plasma membrane functions. Blood 74, 1844-1851.
30. Johnstone, R. M., Mathew, A., Mason, A. B., and Teng, K. (1991). Exosome formation during maturation of mammalian and avian reticulocytes: evidence that exosome release is a major route for externalization of obsolete membrane proteins. J. Cell. Physiol. 147, 27-36.
31. Jung, T., Castellana, D., Klingbeil, P., Cuesta Hernandez, I., Vitacolonna, M., Orlicky, D. J., Roffler, S. R., Brodt, P., and Zoller, M. (2009). CD44v6 dependence of premetastatic niche preparation by exosomes. Neoplasia 11, 1093-1105.
32. Kakisaka, T., Kondo, T., Okano, T., Fujii, K., Honda, K., Endo, M., Tsuchida, A., Aoki, T., Itoi, T., Moriyasu, F., Yamada, T., Kato, H., Nishimura, T., Todo, S., and Hirohashi, S. (2007). Plasma proteomics of pancreatic cancer patients by multi-dimensional liquid chromatography and two-dimensional difference gel electrophoresis (2D-DIGE): up-regulation of leucine-rich alpha-2-glycoprotein in pancreatic cancer. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 852, 257-267.
33. Keller, S., Ridinger, J., Rupp, A. K., Janssen, J. W., and Altevogt, P. (2011). Body fluid derived exosomes as a novel template for clinical diagnostics. J. Transl. Med. 9, 86.
34. Kosaka, N., Iguchi, H., Yoshioka, Y., Takeshita, F., Matsuki, Y., and Ochiya, T. (2010). Secretory mechanisms and intercellular transfer of microRNAs in living cells. J. Biol. Chem. 285, 17442-17452.
35. Lagos-Quintana, M., Rauhut, R., Lendeckel, W., and Tuschl, T. (2001). Identification of novel genes coding for small expressed RNAs. Science 294, 853-858.
36. Lee, E. J., Gusev, Y., Jiang, J., Nuovo, G. J., Lerner, M. R., Frankel, W. L., Morgan, D. L., Postier, R. G., Brackett, D. J., and Schmittgen, T. D. (2007). Expression profiling identifies microRNA signature in pancreatic cancer. Int. J. Cancer 120, 1046-1054.
37. Lee, Y. S., Kim, S. H., Cho, J. A., and Kim, C. W. (2011). Introduction of the CIITA gene into tumor cells produces exosomes with enhanced anti-tumor effects. Exp. Mol. Med. 43, 281-290.
38. Li, J., Sherman-Baust, C. A., Tsai-Turton, M., Bristow, R. E., Roden, R. B., and Morin, P. J. (2009). Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer. BMC Cancer 9, 244. doi:10.1186/1471-2407-9-244
39. Li, Q. L., Bu, N., Yu, Y. C., Hua, W., and Xin, X. Y. (2008). Exvivo experiments of human ovarian cancer ascites-derived exosomes presented by dendritic cells derived from umbilical cord blood for immunotherapy treatment. Clin. Med. Oncol. 2, 461-467.
40. Li, X. B., Zhang, Z. R., Schluesener, H. J., and Xu, S. Q. (2006). Role of exosomes in immune regulation. J. Cell. Mol. Med. 10, 364-375.
41. Li, Y., Zhang, Y., Qiu, F., and Qiu, Z. (2011). Proteomic identification of exosomal LRG1: a potential urinary biomarker for detecting NSCLC. Electrophoresis 32, 1976-1983.
42. Logozzi, M., De Milito, A., Lugini, L., Borghi, M., Calabro, L., Spada, M., Perdicchio, M., Marino, M. L., Federici, C., Iessi, E., Brambilla, D., Venturi, G., Lozupone, F., Santinami, M., Huber, V., Maio, M., Rivoltini, L., and Fais, S. (2009). High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients. PLoS ONE 4, e5219. doi:10.1371/journal.pone.0005219
43. Loomis, R. J., Holmes, D. A., Elms, A., Solski, P. A., Der, C. J., and Su, L. (2006). Citron kinase, a RhoA effector, enhances HIV-1 virion production by modulating exocytosis. Traffic 7, 1643-1653.
44. Lu, Q., Zhang, J., Allison, R., Gay, H., Yang, W. X., Bhowmick, N. A., Frelix, G., Shappell, S., and Chen, Y. H. (2009). Identification of extracellular delta-catenin accumulation for prostate cancer detection. Prostate 69, 411-418.
45. Mathew, A., Bell, A., and Johnstone, R. M. (1995). Hsp-70 is closely associated with the transferrin receptor in exosomes from maturing reticulocytes. Biochem. J. 308(Pt 3), 823-830.
46. Mathivanan, S., Fahner, C. J., Reid, G. E., and Simpson, R. J. (2012). ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic Acids Res. 40, D1241-D1244.
47. Mathivanan, S., and Simpson, R. J. (2009). ExoCarta: a compendium of exosomal proteins and RNA. Proteomics 9, 4997-5000.
48. McCready, J., Sims, J. D., Chan, D., and Jay, D. G. (2010). Secretion of extracellular hsp90alpha via exosomes increases cancer cell motility: a role for plasminogen activation. BMC Cancer 10, 294. doi:10.1186/1471-2407-10-294
49. Meckes, D. G. Jr., Shair, K. H., Marquitz, A. R., Kung, C. P., Edwards, R. H., and Raab-Traub, N. (2010). Human tumor virus utilizes exosomes for intercellular communication. Proc. Natl. Acad. Sci. U.S.A. 107, 20370-20375.
50. Mitchell, J. P., Court, J., Mason, M. D., Tabi, Z., and Clayton, A. (2008). Increased exosome production from tumour cell cultures using the Integra CELLine Culture System. J. Immunol. Methods 335, 98-105.
51. Navabi, H., Croston, D., Hobot, J., Clayton, A., Zitvogel, L., Jasani, B., Bailey-Wood, R., Wilson, K., Tabi, Z., Mason, M. D., and Adams, M. (2005). Preparation of human ovarian cancer ascites-derived exosomes for a clinical trial. Blood Cells Mol. Dis. 35, 149-152.
52. Nazarenko, I., Rana, S., Baumann, A., Mcalear, J., Hellwig, A., Trendelenburg, M., Lochnit, G., Preissner, K. T., and Zoller, M. (2010). Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation. Cancer Res. 70, 1668-1678.
53. Ochieng, J., Pratap, S., Khatua, A. K., and Sakwe, A. M. (2009). Anchorage-independent growth of breast carcinoma cells is mediated by serum exosomes. Exp. Cell Res. 315, 1875-1888.
54. Ogawa, Y., Kanai-Azuma, M., Akimoto, Y., Kawakami, H., and Yanoshita, R. (2008). Exosome-like vesicles with dipeptidyl peptidase IV in human saliva. Biol. Pharm. Bull. 31, 1059-1062.
55. Ohshima, K., Inoue, K., Fujiwara, A., Hatakeyama, K., Kanto, K., Watanabe, Y., Muramatsu, K., Fukuda, Y., Ogura, S., Yamaguchi, K., and Mochizuki, T. (2010). Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PLoS ONE 5, e13247. doi:10.1371/journal.pone.0013247
56. Ostrowski, M., Carmo, N. B., Krumeich, S., Fanget, I., Raposo, G., Savina, A., Moita, C. F., Schauer, K., Hume, A. N., Freitas, R. P., Goud, B., Benaroch, P., Hacohen, N., Fukuda, M., Desnos, C., Seabra, M. C., Darchen, F., Amigorena, S., Moita, L. F., and Thery, C. (2010). Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol. 12, 19-30; sup pp. 11-13.
57. Park, J. E., Tan, H. S., Datta, A., Lai, R. C., Zhang, H., Meng, W., Lim, S. K., and Sze, S. K. (2010). Hypoxic tumor cell modulates its microenvironment to enhance angiogenic and metastatic potential by secretion of proteins and exosomes. Mol. Cell. Proteomics 9, 1085-1099.
58. Pisitkun, T., Shen, R. F., and Knepper, M. A. (2004). Identification and proteomic profiling of exosomes in human urine. Proc. Natl. Acad. Sci. U.S.A. 101, 13368-13373.
59. Ponnambalam, S., and Baldwin, S. A. (2003). Constitutive protein secretion from the trans-Golgi network to the plasma membrane. Mol. Membr. Biol. 20, 129-139.
60. Qu, J. L., Qu, X. J., Zhao, M. F., Teng, Y. E., Zhang, Y., Hou, K. Z., Jiang, Y. H., Yang, X. H., and Liu, Y. P. (2009). The role of cbl family of ubiquitin ligases in gastric cancer exosome-induced apoptosis of Jurkat T cells. Acta Oncol. (Madr.) 48, 1173-1180.
61. Rajashekhar, G., Willuweit, A., Patterson, C. E., Sun, P., Hilbig, A., Breier, G., Helisch, A., and Clauss, M. (2006). Continuous endothelial cell activation increases angiogenesis: evidence for the direct role of endothelium linking angiogenesis and inflammation. J. Vasc. Res. 43, 193-204.
62. Rajendran, L., Honsho, M., Zahn, T. R., Keller, P., Geiger, K. D., Verkade, P., and Simons, K. (2006). Alzheimer's disease beta-amyloid peptides are released in association with exosomes. Proc. Natl. Acad. Sci. U.S.A. 103, 11172-11177.
63. Ratajczak, J., Miekus, K., Kucia, M., Zhang, J., Reca, R., Dvorak, P., and Ratajczak, M. Z. (2006). Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20, 847-856.
64. Record, M., Subra, C., Silvente-Poirot, S., and Poirot, M. (2011). Exosomes as intercellular signalosomes and pharmacological effectors. Biochem. Pharmacol. 81, 1171-1182.
65. Ristorcelli, E., Beraud, E., Verrando, P., Villard, C., Lafitte, D., Sbarra, V., Lombardo, D., and Verine, A. (2008). Human tumor nanoparticles induce apoptosis of pancreatic cancer cells. FASEB J. 22, 3358-3369.
66. Roldo, C., Missiaglia, E., Hagan, J. P., Falconi, M., Capelli, P., Bersani, S., Calin, G. A., Volinia, S., Liu, C. G., Scarpa, A., and Croce, C. M. (2006). MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J. Clin. Oncol. 24, 4677-4684.
67. Rosell, R., Wei, J., and Taron, M. (2009). Circulating microRNA signatures of tumor-derived exosomes for early diagnosis of non-small-cell lung cancer. Clin Lung Cancer 10, 8-9.
68. Saxena, N., Lahiri, S. S., Hambarde, S., and Tripathi, R. P. (2008). RAS: target for cancer therapy. Cancer Invest. 26, 948-955.
69. Shi, L., Chen, J., Yang, J., Pan, T., Zhang, S., and Wang, Z. (2010). MiR-21 protected human glioblastoma U87MG cells from chemotherapeutic drug temozolomide induced apoptosis by decreasing Bax/Bcl-2 ratio and caspase-3 activity. Brain Res. 1352, 255-264.
70. Simpson, R. J., Jensen, S. S., and Lim, J. W. (2008). Proteomic profiling of exosomes: current perspectives. Proteomics 8, 4083-4099.
71. Skog, J., Wurdinger, T., Van Rijn, S., Meijer, D. H., Gainche, L., Sena-Esteves, M., Curry, W. T. Jr., Carter, B. S., Krichevsky, A. M., and Breakefield, X. O. (2008). Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat. Cell Biol. 10, 1470-1476.
72. Smith, D. S., Humphrey, P. A., and Catalona, W. J. (1997). The early detection of prostate carcinoma with prostate specific antigen: the Washington University experience. Cancer 80, 1852-1856.
73. Staubach, S., Razawi, H., and Hanisch, F. G. (2009). Proteomics of MUC1-containing lipid rafts from plasma membranes and exosomes of human breast carcinoma cells MCF-7. Proteomics 9, 2820-2835.
74. Taieb, J., Chaput, N., Schartz, N., Roux, S., Novault, S., Menard, C., Ghiringhelli, F., Terme, M., Carpentier, A. F., Darrasse-Jeze, G., Lemonnier, F., and Zitvogel, L. (2006). Chemoimmunotherapy of tumors: cyclophosphamide synergizes with exosome based vaccines. J. Immunol. 176, 2722-2729.
75. Takamizawa, J., Konishi, H., Yanagisawa, K., Tomida, S., Osada, H., Endoh, H., Harano, T., Yatabe, Y., Nagino, M., Nimura, Y., Mitsudomi, T., and Takahashi, T. (2004). Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 64, 3753-3756.
76. Tan, A., De La Pena, H., and Seifalian, A. M. (2010). The application of exosomes as a nanoscale cancer vaccine. Int. J. Nanomedicine 5, 889-900.
77. Tavoosidana, G., Ronquist, G., Darmanis, S., Yan, J., Carlsson, L., Wu, D., Conze, T., Ek, P., Semjonow, A., Eltze, E., Larsson, A., Landegren, U. D., and Kamali-Moghaddam, M. (2011). Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer. Proc. Natl. Acad. Sci. U.S.A. 108, 8809-8814.
78. Taylor, D. D., and Gercel-Taylor, C. (2008). MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol. Oncol. 110, 13-21.
79. Taylor, D. D., Zacharias, W., and Gercel-Taylor, C. (2011). Exosome isolation for proteomic analyses and RNA profiling. Methods Mol. Biol. 728, 235-246.
80. Thery, C. (2011). Exosomes: secreted vesicles and intercellular communications. F1000 Biol. Rep. 3, 15.
81. Thery, C., Zitvogel, L., and Amigorena, S. (2002). Exosomes: composition, biogenesis and function. Nat. Rev. Immunol. 2, 569-579.
82. Valadi, H., Ekstrom, K., Bossios, A., Sjostrand, M., Lee, J. J., and Lotvall, J. O. (2007). Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9, 654-659.
83. Welton, J. L., Khanna, S., Giles, P. J., Brennan, P., Brewis, I. A., Staffurth, J., Mason, M. D., and Clayton, A. (2010). Proteomics analysis of bladder cancer exosomes. Mol. Cell. Proteomics 9, 1324-1338.
84. Yang, C., and Robbins, P. D. (2011). The roles of tumor-derived exosomes in cancer pathogenesis. Clin. Dev. Immunol. 2011, 842849.
85. Yu, X., Harris, S. L., and Levine, A. J. (2006). The regulation of exosome secretion: a novel function of the p53 protein. Cancer Res. 66, 4795-4801.
86. Zhang, Y., Luo, C. L., He, B. C., Zhang, J. M., Cheng, G., and Wu, X. H. (2010). Exosomes derived from IL-12-anchored renal cancer cells increase induction of specific antitumor response in vitro: a novel vaccine for renal cell carcinoma. Int. J. Oncol. 36, 133-140.
87. Zhou, Q., Li, M., Wang, X., Li, Q., Wang, T., Zhu, Q., Zhou, X., Gao, X., and Li, X. (2012). Immune-related microRNAs are abundant in breast milk exosomes. Int. J. Biol. Sci. 8, 118-123.
88. Zomer, A., Vendrig, T., Hopmans, E. S., Van Eijndhoven, M., Middeldorp, J. M., and Pegtel, D. M. (2010). Exosomes: fit to deliver small RNA. Commun. Integr. Biol. 3, 447-450.