Extracellular vesicles - biomarkers and effectors of the cellular interactome in cancer

Frontiers in Pharmacology

Volumn 4 MAR, Issue , 2013, Pages

  Rak, Janusz ^a  

^a RESEARCH INSTITUTE OF THE MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

Author keywords

Cancer; Cellular interactions; Exosomes; Extracellular vesicles; Oncogenes

Indexed keywords

ADENOSINE DIPHOSPHATE RIBOSYLATION FACTOR 6; BEVACIZUMAB; BIOLOGICAL MARKER; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; HEAT SHOCK PROTEIN 70; IMATINIB; INTERLEUKIN 18; K RAS PROTEIN; MATRIX METALLOPROTEINASE; MICRORNA; MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE 2; ONCOPROTEIN; PHOSPHOPROTEIN; PROTEIN KINASE B; RAS PROTEIN; RHO FACTOR; SUNITINIB; TRASTUZUMAB; TUMOR SUPPRESSOR PROTEIN; VEMURAFENIB; BIOACTIVE LIPID; DNA; GROWTH FACTOR; LIPID; MUTANT PROTEIN; PROTEINASE; TUMOR MARKER; UNCLASSIFIED DRUG;

ANGIOGENESIS; APOPTOSIS; BLOOD CLOTTING DISORDER; BREAST CANCER; CANCER CELL; CELL COMMUNICATION; CELL MIGRATION; CELL TRANSFORMATION; CELL VACUOLE; CHRONIC MYELOID LEUKEMIA; CLASSIFIER; COLORECTAL CANCER; DNA SEQUENCE; DRUG RESISTANCE; ENZYME INHIBITION; EXOSOME; EXTRACELLULAR VESICLE; HUMAN; IMMUNITY; INFLAMMATION; KIDNEY CANCER; MALIGNANT NEOPLASTIC DISEASE; MELANOMA; MEMBRANE STRUCTURE; METASTASIS; MOLECULAR DYNAMICS; NONHUMAN; PHENOTYPE; REVIEW; TUMOR MICROENVIRONMENT; APOPTOTIC BODY; BODY FLUID; BONE MARROW CELL; CANCER DIAGNOSIS; CANCER PATIENT; CANCER THERAPY; CELL FUNCTION; CELL INTERACTION; CELL ORGANELLE; CELLULAR INTERACTOME; CELLULAR STEMNESS; DISEASE MARKER; DRUG TARGETING; ECTOSOME; EXTRACELLULAR SPACE; GENE MUTATION; MICROENVIRONMENT; NANOTECHNOLOGY; ONCOGENE; ONCOSOME; PHENOTYPIC REPROGRAMING;

EID: 84879535955     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2013.00021     Document Type: Review

References (139)

1. Abid Hussein, M. N., Boing, A. N., Sturk, A., Hau, C. M., and Nieuwland, R. (2007). Inhibition of microparticle release triggers endothelial cell apoptosis and detachment. Thromb. Haemost. 98, 1096-1107.
2. Al-Nedawi, K., Meehan, B., Micaleff, J., Guha, A., and Rak, J. (2010). Phosphoproteome of tumour derived microvesicles as a source of biomarkers to monitor the effects of targeted agents in glioblastoma. Society of Neurooncology, Annual Meeting, Montreal.
3. Al-Nedawi, K., Meehan, B., Kerbel, R. S., Allison, A. C., and Rak, J. (2009). Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR. Proc. Natl. Acad. Sci. U.S.A. 106, 3794-3799.
4. Al-Nedawi, K., Meehan, B., Micallef, J., Lhotak, V., May, L., Guha, A., et al. (2008). Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat. Cell Biol. 10, 619-624.
5. Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., and Wood, M. J. (2011). Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 29, 341-345.
6. Andre, F., Escudier, B., Angevin, E., Tursz, T., and Zitvogel, L. (2004). Exosomes for cancer immunotherapy. Ann. Oncol. 15(Suppl. 4), iv141-iv144.
7. Antonyak, M. A., Li, B., Boroughs, L. K., Johnson, J. L., Druso, J. E., Bryant, K. L., et al. (2011). Cancer cell-derived microvesicles induce transformation by transferring tissue transglutaminase and fibronectin to recipient cells. Proc. Natl. Acad. Sci. U.S.A. 108, 4852-4857.
8. Avraham, R., and Yarden, Y. (2011). Feedback regulation of EGFR signalling: decision making by early and delayed loops. Nat. Rev. Mol. Cell Biol. 12, 104-117.
9. Balaj, L., Lessard, R., Dai, L., Cho, Y. J., Pomeroy, S. L., Breakefield, X. O., et al. (2011). Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat. Commun. 2, 180.
10. Bebawy, M., Combes, V., Lee, E., Jaiswal, R., Gong, J., Bonhoure, A., et al. (2009). Membrane microparticles mediate transfer of P-glycoprotein to drug sensitive cancer cells. Leukemia 23, 1643-1649.
11. Bergers, G., and Hanahan, D. (2008). Modes of resistance to anti-angiogenic therapy. Nat. Rev. Cancer 8, 592-603.
12. Bergsmedh, A., Szeles, A., Henriksson, M., Bratt, A., Folkman, M. J., Spetz, A. L., et al. (2001). Horizontal transfer of oncogenes by uptake of apoptotic bodies. Proc. Natl. Acad. Sci. U.S.A. 98, 6407-6411.
13. Bianco, F., Perrotta, C., Novellino, L., Francolini, M., Riganti, L., Menna, E., et al. (2009). Acid sphingomyelinase activity triggers microparticle release from glial cells. EMBO J. 28, 1043-1054.
14. Biernat, W., Huang, H., Yokoo, H., Kleihues, P., and Ohgaki, H. (2004). Predominant expression of mutant EGFR (EGFRvIII) is rare in primary glioblastomas. Brain Pathol. 14, 131-136.
15. Bigner, S. H., Humphrey, P. A., Wong, A. J., Vogelstein, B., Mark, J., Friedman, H. S., et al. (1990). Characterization of the epidermal growth factor receptor in human glioma cell lines and xenografts. Cancer Res. 50, 8017-8022.
16. Bobrie, A., Krumeich, S., Reyal, F., Recchi, C., Moita, L. F., Seabra, M. C., et al. (2012). Rab27a supports exosome-dependent and -independent mechanisms that modify the tumor microenvironment and can promote tumor progression. Cancer Res. 72, 4920-4930.
17. Broxterman, H. J., Lankelma, J., and Hoekman, K. (2003). Resistance to cytotoxic and anti-angiogenic anticancer agents: similarities and differences. Drug Resist. Updat. 6, 111-127.
18. Camussi, G., Deregibus, M. C., Bruno, S., Cantaluppi, V., and Biancone, L. (2010). Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int. 78, 838-848.
19. Chairoungdua, A., Smith, D. L., Pochard, P., Hull, M., and Caplan, M. J. (2010). Exosome release of beta-catenin: a novel mechanism that antagonizes Wnt signaling. J. Cell Biol. 190, 1079-1091.
20. Chiang, A. C., and Massague, J. (2008). Molecular basis of metastasis. N. Engl. J. Med. 359, 2814-2823.
21. Ciravolo, V., Huber, V., Ghedini, G. C., Venturelli, E., Bianchi, F., Campiglio, M., et al. (2012). Potential role of HER2-overexpressing exosomes in countering trastuzumab-based therapy. J. Cell. Physiol. 227, 658-667.
22. Cronan, M. R., Nakamura, K., Johnson, N. L., Granger, D. A., Cuevas, B. D., Wang, J. G., et al. (2012). Defining MAP3 kinases required for MDA-MB-231 cell tumor growth and metastasis. Oncogene 31, 3889-3900.
23. Curtis, C., Shah, S. P., Chin, S. F., Turashvili, G., Rueda, O. M., Dunning, M. J., et al. (2012). The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486, 346-352.
24. Demory, B. M., Higginbotham, J. N., Franklin, J. L., Ham, A. J., Halvey, P. J., Imasuen, I. E., et al. (2012). Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS. Mol. Cell Proteomics 12, 343-355.
25. Deregibus, M. C., Cantaluppi, V., Calogero, R., Lo, I. M., Tetta, C., Biancone, L., et al. (2007). Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 110, 2440-2448.
26. Di Vizio, D., Kim, J., Hager, M. H., Morello, M., Yang, W., Lafargue, C. J., et al. (2009). Oncosome formation in prostate cancer: association with a region of frequent chromosomal deletion in metastatic disease. Cancer Res. 69, 5601-5609.
27. Diamant, M., Tushuizen, M. E., Sturk, A., and Nieuwland, R. (2004). Cellular microparticles: new players in the field of vascular disease? Eur. J. Clin. Invest. 34, 392-401.
28. Dick, J. E. (2008). Stem cell concepts renew cancer research. Blood 112, 4793-4807.
29. Dolberg, D. S., and Bissell, M. J. (1984). Inability of Rous sarcoma virus to cause sarcomas in the avian embryo. Nature 309, 552-556.
30. Dolo, V., D'Ascenzo, S., Giusti, I., Millimaggi, D., Taraboletti, G., and Pavan, A. (2005). Shedding of membrane vesicles by tumor and endothelial cells. Ital. J. Anat. Embryol. 110, 127-133.
31. Druker, B. J. (2004). Imatinib as a paradigm of targeted therapies. Adv. Cancer Res. 91, 1-30.
32. El-Andaloussi, S., Lee, Y., Lakhal-Littleton, S., Li, J., Seow, Y., Gardiner, C., et al. (2012). Exosome-mediated delivery of siRNA in vitro and in vivo. Nat. Protoc. 7, 2112-2126.
33. Fichtlscherer, S., Zeiher, A. M., and Dimmeler, S. (2011). Circulating microRNAs: biomarkers or mediators of cardiovascular diseases? Arterioscler. Thromb. Vasc. Biol. 31, 2383-2390.
34. Fidler, I. J. (2003). The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat. Rev. Cancer 3, 453-458.
35. Finak, G., Bertos, N., Pepin, F., Sadekova, S., Souleimanova, M., Zhao, H., et al. (2008). Stromal gene expression predicts clinical outcome in breast cancer. Nat. Med. 14, 518-527.
36. Flaherty, K. T., Hodi, F. S., and Fisher, D. E. (2012). From genes to drugs: targeted strategies for melanoma. Nat. Rev. Cancer 12, 349-361.
37. Folkman, J., and Kalluri, R. (2003). "Tumor angiogenesis," in Cancer Medicine, eds D. W. Kufe, R. E. Pollock, R. R. Weichselbaum, R. C. Jr. Bast, T. S. Gansler, J. F. Holland, and E. III Frei (Hamilton: BC Decker Inc.), 161-194.
38. Furie, B., and Furie, B. C. (2004). Role of platelet P-selectin and microparticle PSGL-1 in thrombus formation. Trends Mol. Med. 10, 171-178.
39. Garcia-Barros, M., Paris, F., Cordon-Cardo, C., Lyden, D., Rafii, S., Haimovitz-Friedman, A., et al. (2003). Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science 300, 1155-1159.
40. Garnier, D., Magnus, N., Lee, T. H., Bentley, V., Meehan, B., Milsom, C., et al. (2012). Cancer cells induced to express mesenchymal phenotype release exosome-like extracellular vesicles carrying tissue factor. J. Biol. Chem. 287, 43565-43572.
41. Gerlinger, M., Rowan, A. J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., et al. (2012). Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 366, 883-892.
42. 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.
43. Ghosh, A. K., Secreto, C. R., Knox, T. R., Ding, W., Mukhopadhyay, D., and Kay, N. E. (2010). Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: implications for disease progression. Blood 115, 1755-1764.
44. Gonzales, P. A., Pisitkun, T., Hoffert, J. D., Tchapyjnikov, D., Star, R. A., Kleta, R., et al. (2009). Large-scale proteomics and phosphoproteomics of urinary exosomes. J. Am. Soc. Nephrol. 20, 363-379.
45. Graner, M. W., Alzate, O., Dechkovskaia, A. M., Keene, J. D., Sampson, J. H., Mitchell, D. A., et al. (2009). Proteomic and immunologic analyses of brain tumor exosomes. FASEB J. 23, 1541-1557.
46. Greaves, M., and Maley, C. C. (2012). Clonal evolution in cancer. Nature 481, 306-313.
47. Greco, F., Ciana, A., Pietra, D., Balduini, C., Minetti, G., and Torti, M. (2006). Rap2, but not Rap1 GTPase is expressed in human red blood cells and is involved in vesiculation. Biochim. Biophys. Acta 1763, 330-335.
48. Gross, J. C., Chaudhary, V., Bartscherer, K., and Boutros, M. (2012). Active Wnt proteins are secreted on exosomes. Nat. Cell Biol. 14, 1036-1045.
49. Hanahan, D., and Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell 144, 646-674.
50. Hao, S., Ye, Z., Li, F., Meng, Q., Qureshi, M., Yang, J., et al. (2006). Epigenetic transfer of metastatic activity by uptake of highly metastatic B16 melanoma cell-released exosomes. Exp. Oncol. 28, 126-131.
51. Hendrix, A., Maynard, D., Pauwels, P., Braems, G., Denys, H., Van den Broecke, R., et al. (2010). Effect of the secretory small GTPase Rab27B on breast cancer growth, invasion, and metastasis. J. Natl. Cancer Inst. 102, 866-880.
52. Heppner, G. H. (1989). Tumor cell societies. J. Natl. Cancer Inst. 81, 648-649.
53. Hida, K., Hida, Y., Amin, D. N., Flint, A. F., Panigrahy, D., Morton, C. C., et al. (2004). Tumor-associated endothelial cells with cytogenetic abnormalities. Cancer Res. 64, 8249-8255.
54. Hill, R., Song, Y., Cardiff, R. D., and Van Dyke, T. (2005). Selective evolution of stromal mesenchyme with p53 loss in response to epithelial tumorigenesis. Cell 123, 1001-1011.
55. Holmgren, L. (2010). Horizontal gene transfer: you are what you eat. Biochem. Biophys. Res. Commun. 396, 147-151.
56. Hood, J. L., San, R. S., and Wickline, S. A. (2011). Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res. 71, 3792-3801.
57. Hunter, K. (2006). Host genetics influence tumour metastasis. Nat. Rev. Cancer 6, 141-146.
58. Huse, J. T., and Holland, E. C. (2009). Genetically engineered mouse models of brain cancer and the promise of preclinical testing. Brain Pathol. 19, 132-143.
59. Inda, M. M., Bonavia, R., Mukasa, A., Narita, Y., Sah, D. W., Vandenberg, S., et al. (2010). Tumor heterogeneity is an active process maintained by a mutant EGFR-induced cytokine circuit in glioblastoma. Genes Dev. 24, 1731-1745.
60. Jaiswal, R., Gong, J., Sambasivam, S., Combes, V., Mathys, J. M., Davey, R., et al. (2011). Microparticle-associated nucleic acids mediate trait dominance in cancer. FASEB J. 26, 420-429.
61. Janowska-Wieczorek, A., Wysoczynski, M., Kijowski, J., Marquez-Curtis, L., Machalinski, B., Ratajczak, J., et al. (2005). Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int. J. Cancer 113, 752-760.
62. Johnstone, R. M. (2006). Exosomes biological significance: a concise review. Blood Cells Mol. Dis. 36, 315-321.
63. Jung, T., Castellana, D., Klingbeil, P., Cuesta, H. I., Vitacolonna, M., Orlicky, D. J., et al. (2009). CD44v6 dependence of premetastatic niche preparation by exosomes. Neoplasia 11, 1093-1105.
64. Kalra, H., Simpson, R. J., Ji, H., Aikawa, E., Altevogt, P., Askenase, P., et al. (2012). Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLoS Biol. 10:e1001450. doi:10.1371/journal.pbio.100145022.
65. Kaplan, R. N., Riba, R. D., Zacharoulis, S., Bramley, A. H., Vincent, L., Costa, C., et al. (2005). VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438, 820-827.
66. Koga, K., Matsumoto, K., Akiyoshi, T., Kubo, M., Yamanaka, N., Tasaki, A., et al. (2005). Purification, characterization and biological significance of tumor-derived exosomes. Anticancer Res. 25, 3703-3707.
67. Kosaka, N., Iguchi, H., and Ochiya, T. (2010). Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 101, 2087-2092.
68. Lee, T. H., Montermini, L., Meehan, B., Guha, A., and Rak, J. (2011). "Microvesicles as intercellular messengers carrying oncogenic and tumour suppressory signals," in Poster Presentation, The Canadian Cancer Research Conference, Toronto, ON.
69. Lespagnol, A., Duflaut, D., Beekman, C., Blanc, L., Fiucci, G., Marine, J. C., et al. (2008). Exosome secretion, including the DNA damage-induced p53-dependent secretory pathway, is severely compromised in TSAP6/Steap3-null mice. Cell Death Differ. 15, 1723-1733.
70. Li, B., Antonyak, M. A., Zhang, J., and Cerione, R. A. (2012). RhoA triggers a specific signaling pathway that generates transforming microvesicles in cancer cells. Oncogene 31, 4740-4749.
71. Linardou, H., Dahabreh, I. J., Bafaloukos, D., Kosmidis, P., and Murray, S. (2009). Somatic EGFR mutations and efficacy of tyrosine kinase inhibitors in NSCLC. Nat. Rev. Clin. Oncol. 6, 352-366.
72. Luga, V., Zhang, L., Viloria-Petit, A. M., Ogunjimi, A. A., Inanlou, M. R., Chiu, E., et al. (2012). Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell 151, 1542-1556.
73. Marleau, A. M., Chen, C. S., Joyce, J. A., and Tullis, R. H. (2012). Exosome removal as a therapeutic adjuvant in cancer. J. Transl. Med. 10, 134.
74. Marzesco, A. M., Janich, P., Wilsch-Brauninger, M., Dubreuil, V., Langenfeld, K., Corbeil, D., et al. (2005). Release of extracellular membrane particles carrying the stem cell marker prominin-1 (CD133) from neural progenitors and other epithelial cells. J. Cell. Sci. 118, 2849-2858.
75. McAllister, S. S., Gifford, A. M., Greiner, A. L., Kelleher, S. P., Saelzler, M. P., Ince, T. A., et al. (2008). Systemic endocrine instigation of indolent tumor growth requires osteopontin. Cell 133, 994-1005.
76. 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.
77. Mellinghoff, I. K., Wang, M. Y., Vivanco, I., Haas-Kogan, D. A., Zhu, S., Dia, E. Q., et al. (2005). Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N. Engl. J. Med. 353, 2012-2024.
78. Miller, F. R., and Heppner, G. H. (1990). Cellular interactions in metastasis. Cancer Metastasis Rev. 9, 21-34.
79. Mintz, B., and Illmensee, K. (1975). Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc. Natl. Acad. Sci. U.S.A. 72, 3585-3589.
80. Muller, G. (2012). Microvesicles/exosomes as potential novel biomarkers of metabolic diseases. Diabetes Metab. Syndr. Obes. 5, 247-282.
81. Muralidharan-Chari, V., Clancy, J., Plou, C., Romao, M., Chavrier, P., Raposo, G., et al. (2009). ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr. Biol. 19, 1875-1885.
82. Murdoch, D., and Sager, J. (2008). Will targeted therapy hold its promise? An evidence-based review. Curr. Opin. Oncol. 20, 104-111.
83. Noerholm, M., Balaj, L., Limperg, T., Salehi, A., Zhu, L. D., Hochberg, F. H., et al. (2012). RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls. BMC Cancer 12:22. doi:10.1186/1471-2407-12-22
84. Nowell, P. C. (1976). The clonal evolution of tumor cell populations. Science 194, 23-28.
85. Ohno, S. I., Takanashi, M., Sudo, K., Ueda, S., Ishikawa, A., Matsuyama, N., et al. (2012). Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol. Ther. 21, 185-191.
86. Ostrowski, M., Carmo, N. B., Krumeich, S., Fanget, I., Raposo, G., Savina, A., et al. (2010). Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol. 12, 19-30.
87. Paget, S. (1889). The distribution of secondary growths in cancer of the breast. Lancet 1, 571-573.
88. Palma, J., Yaddanapudi, S. C., Pigati, L., Havens, M. A., Jeong, S., Weiner, G. A., et al. (2012). MicroRNAs are exported from malignant cells in customized particles. Nucleic Acids Res. 40, 9125-9138.
89. Pegtel, D. M., Cosmopoulos, K., Thorley-Lawson, D. A., van Eijndhoven, M. A., Hopmans, E. S., Lindenberg, J. L., et al. (2010). Functional delivery of viral miRNAs via exosomes. Proc. Natl. Acad. Sci. U.S.A. 107, 6328-6333.
90. Peinado, H., Aleckovic, M., Lavotshkin, S., Matei, I., Costa-Silva, B., Moreno-Bueno, G., et al. (2012). Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat. Med. 18, 833-891.
91. Phillips, H. S., Kharbanda, S., Chen, R., Forrest, W. F., Soriano, R. H., Wu, T. D., et al. (2006). Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9, 157-173.
92. Piccin, A., Murphy, W. G., and Smith, O. P. (2007). Circulating microparticles: pathophysiology and clinical implications. Blood Rev. 21, 157-171.
93. Poste, G., and Nicolson, G. L. (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.
94. Putz, U., Howitt, J., Doan, A., Goh, C. P., Low, L. H., Silke, J., et al. (2012). The tumor suppressor PTEN is exported in exosomes and has phosphatase activity in recipient cells. Sci. Signal. 5, ra70.
95. Qian, B. Z., and Pollard, J. W. (2010). Macrophage diversity enhances tumor progression and metastasis. Cell 141, 39-51.
96. Rak, J. (2006). Is cancer stem cell a cell, or a multicellular unit capable of inducing angiogenesis? Med. Hypotheses 66, 601-604.
97. Rak, J., and Guha, A. (2012). Extracellular vesicles-vehicles that spread cancer genes. Bioessays 34, 489-497.
98. Ramachandran, A., Yan, H., Bentink, S., Noerholm, M., Berking, C., Flaherty, K., et al. (2011). Detection of BRAF mutations in serum/plasma microvesicles (exosomes) of malignant melanoma patients in Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, San Francisco, CA. Mol. Cancer Ther. 10(Suppl. 11), Abstract nr C139.
99. Ramnarain, D. B., Park, S., Lee, D. Y., Hatanpaa, K. J., Scoggin, S. O., Otu, H., et al. (2006). Differential gene expression analysis reveals generation of an autocrine loop by a mutant epidermal growth factor receptor in glioma cells. Cancer Res. 66, 867-874.
100. 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.
101. Record, M., Subra, C., Silvente-Poirot, S., and Poirot, M. (2011). Exosomes as intercellular signalosomes and pharmacological effectors. Biochem. Pharmacol. 81, 1171-1182.
102. Revesz, L. (1956). Effect of tumour cells killed by x-rays upon the growth of admixed viable cells. Nature 178, 1391-1392.
103. Ritter, C. A., Perez-Torres, M., Rinehart, C., Guix, M., Dugger, T., Engelman, J. A., et al. (2007). Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network. Clin. Cancer Res. 13, 4909-4919.
104. Roy, S., Hsiung, F., and Kornberg, T. B. (2011). Specificity of Drosophila cytonemes for distinct signaling pathways. Science 332, 354-358.
105. Sartori, M. T., Della, P. A., Ballin, A., Saggiorato, G., Bernardi, D., Padoan, A., et al. (2011). Prothrombotic state in glioblastoma multiforme: an evaluation of the procoagulant activity of circulating microparticles. J. Neurooncol. 104, 225-231.
106. Schulte, A., Gunther, H. S., Martens, T., Zapf, S., Riethdorf, S., Wulfing, C., et al. (2012). Glioblastoma stem-like cell lines with either maintenance or loss of high-level EGFR amplification, generated via modulation of ligand concentration. Clin. Cancer Res. 18, 1901-1913.
107. Schwarzenbach, H., Hoon, D. S., and Pantel, K. (2011). Cell-free nucleic acids as biomarkers in cancer patients. Nat. Rev. Cancer 11, 426-437.
108. Shao, H., Chung, J., Balaj, L., Charest, A., Bigner, D. D., Carter, B. S., et al. (2012). Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy. Nat. Med. 1, 26.
109. Sheldon, H., Heikamp, E., Turley, H., Dragovic, R., Thomas, P., Oon, C. E., et al. (2010). New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes. Blood 116, 2385-2394.
110. Siena, S., Sartore-Bianchi, A., Di, N. F., Balfour, J., and Bardelli, A. (2009). Biomarkers predicting clinical outcome of epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer. J. Natl. Cancer Inst. 101, 1308-1324.
111. Skog, J., Wurdinger, T., van Rijn, S., Meijer, D. H., Gainche, L., Curry, W. T. Jr., et al. (2008). Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat. Cell Biol. 10, 1470-1476.
112. Snuderl, M., Fazlollahi, L., Le, L. P., Nitta, M., Zhelyazkova, B. H., Davidson, C. J., et al. (2011). Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma. Cancer Cell 20, 810-817.
113. Stock, K., Kumar, J., Synowitz, M., Petrosino, S., Imperatore, R., Smith, E. S., et al. (2012). Neural precursor cells induce cell death of high-grade astrocytomas through stimulation of TRPV1. Nat. Med. 18, 1232-1238.
114. 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.
115. 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.
116. Taylor, D. D., Zacharias, W., and Gercel-Taylor, C. (2011). Exosome isolation for proteomic analyses and RNA profiling. Methods Mol. Biol. 728, 235-246.
117. Thaler, J., Ay, C., Mackman, N., Bertina, R. M., Kaider, A., Marosi, C., et al. (2012). Microparticle-associated tissue factor activity, venous thromboembolism and mortality in pancreatic, gastric, colorectal and brain cancer patients. J. Thromb. Haemost. 10, 1363-1370.
118. Thery, C., Ostrowski, M., and Segura, E. (2009). Membrane vesicles as conveyors of immune responses. Nat. Rev. Immunol. 9, 581-593.
119. Tolmachova, T., Abrink, M., Futter, C. E., Authi, K. S., and Seabra, M. C. (2007). Rab27b regulates number and secretion of platelet dense granules. Proc. Natl. Acad. Sci. U.S.A. 104, 5872-5877.
120. Trajkovic, K., Hsu, C., Chiantia, S., Rajendran, L., Wenzel, D., Wieland, F., et al. (2008). Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319, 1244-1247.
121. Turner, N. C., and Reis-Filho, J. S. (2012). Genetic heterogeneity and cancer drug resistance. Lancet Oncol. 13, e178-e185.
122. 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.
123. Van Doormaal, F., Kleinjan, A., Berckmans, R. J., Mackman, N., Manly, D., Kamphuisen, P. W., et al. (2012). Coagulation activation and microparticle-associated coagulant activity in cancer patients. An exploratory prospective study. Thromb. Haemost. 108, 160-165.
124. Verderio, C., Muzio, L., Turola, E., Bergami, A., Novellino, L., Ruffini, F., et al. (2012). Myeloid microvesicles are a marker and therapeutic target for neuroinflammation. Ann. Neurol. 72, 610-624.
125. Verweij, F. J., Middeldorp, J. M., and Pegtel, D. M. (2012). Intracellular signaling controlled by the endosomal-exosomal pathway. Commun. Integr. Biol. 5, 88-93.
126. Verweij, F. J., van Eijndhoven, M. A., Hopmans, E. S., Vendrig, T., Wurdinger, T., Cahir-McFarland, E., et al. (2011). LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-kappaB activation. EMBO J. 30, 2115-2129.
127. Vogelstein, B., and Kinzler, K. W. (2004). Cancer genes and the pathways they control. Nat. Med. 10, 789-799.
128. Wang, J. G., Geddings, J. E., Aleman, M. M., Cardenas, J. C., Chantrathammachart, P., Williams, J. C., et al. (2012). Tumor-derived tissue factor activates coagulation and enhances thrombosis in a mouse xenograft model of human pancreatic cancer. Blood 19, 5543-5552.
129. Wen, P. Y., and Kesari, S. (2008). Malignant gliomas in adults. N. Engl. J. Med. 359, 492-507.
130. Wood, L. D., Parsons, D. W., Jones, S., Lin, J., Sjoblom, T., Leary, R. J., et al. (2007). The genomic landscapes of human breast and colorectal cancers. Science 318, 1108-1113.
131. Wu, M., Pastor-Pareja, J. C., and Xu, T. (2010). Interaction between Ras(V12) and scribbled clones induces tumour growth and invasion. Nature 463, 545-548.
132. Wu, X., Northcott, P. A., Dubuc, A., Dupuy, A. J., Shih, D. J., Witt, H., et al. (2012). Clonal selection drives genetic divergence of metastatic medulloblastoma. Nature 482, 529-533.
133. Yang, C., and Robbins, P. D. (2011). The roles of tumor-derived exosomes in cancer pathogenesis. Clin. Dev. Immunol. 2011, 842849.
134. Yu, J. L., May, L., Lhotak, V., Shahrzad, S., Shirasawa, S., Weitz, J. I., et al. (2005). Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis. Blood 105, 1734-1741.
135. 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.
136. Zhang, Y., Roccaro, A. M., Rombaoa, C., Flores, L., Obad, S., Fernandes, S. M., et al. (2012). LNA-mediated anti-miR-155 silencing in low-grade B-cell lymphomas. Blood 120, 1678-1686.
137. Zhou, Z. (2007). New phosphatidylserine receptors: clearance of apoptotic cells and more. Dev. Cell 13, 759-760.
138. Zhuang, X., Xiang, X., Grizzle, W., Sun, D., Zhang, S., Axtell, R. C., et al. (2011). Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol. Ther. 19, 1769-1779.
139. Zwicker, J. I., Trenor, C. C. III, Furie, B. C., and Furie, B. (2011). Tissue factor-bearing microparticles and thrombus formation. Arterioscler. Thromb. Vasc. Biol. 31, 728-733.