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BioMed Research International
Volume 2015 (2015), Article ID 649161, 8 pages
http://dx.doi.org/10.1155/2015/649161
Review Article

The Role of Extracellular Vesicles: An Epigenetic View of the Cancer Microenvironment

1Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
3Department of Neurosurgery, Nanjing Brain Hospital, Nanjing Medical University, No. 264, Guangzhou Road, Nanjing, Jiangsu 210000, China

Received 17 April 2015; Revised 14 July 2015; Accepted 21 July 2015

Academic Editor: Riccardo Alessandro

Copyright © 2015 Zhongrun Qian et al. 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. J. van der Vlist, E. N. M. Nolte-'t Hoen, W. Stoorvogel, G. J. A. Arkesteijn, and M. H. M. Wauben, “Fluorescent labeling of nano-sized vesicles released by cells and subsequent quantitative and qualitative analysis by high-resolution flow cytometry,” Nature Protocols, vol. 7, no. 7, pp. 1311–1326, 2012. View at Publisher · View at Google Scholar · View at Scopus
  2. G. Raposo and W. Stoorvogel, “Extracellular vesicles: exosomes, microvesicles, and friends,” The Journal of Cell Biology, vol. 200, no. 4, pp. 373–383, 2013. View at Publisher · View at Google Scholar · View at Scopus
  3. A. V. G. de Andrade, G. Bertolino, J. Riewaldt et al., “Extracellular vesicles secreted by bone marrow- and adipose tissue-derived mesenchymal stromal cells fail to suppress lymphocyte proliferation,” Stem Cells and Development, vol. 24, no. 11, pp. 1374–1376, 2015. View at Publisher · View at Google Scholar
  4. B. Mytar, M. Baj-Krzyworzeka, M. Majka, D. Stankiewicz, and M. Zembala, “Human monocytes both enhance and inhibit the growth of human pancreatic cancer in SCID mice,” Anticancer Research, vol. 28, no. 1, pp. 187–192, 2008. View at Google Scholar · View at Scopus
  5. 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
  6. H. K. Kim, K. S. Song, Y. S. Park et al., “Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor,” European Journal of Cancer, vol. 39, no. 2, pp. 184–191, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. O. Rechavi, I. Goldstein, and Y. Kloog, “Intercellular exchange of proteins: the immune cell habit of sharing,” FEBS Letters, vol. 583, no. 11, pp. 1792–1799, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. S. D'Agostino, M. Salamone, I. Di Liegro, and M. L. Vittorelli, “Membrane vesicles shed by oligodendroglioma cells induce neuronal apoptosis,” International Journal of Oncology, vol. 29, no. 5, pp. 1075–1085, 2006. View at Google Scholar · View at Scopus
  9. M. C. Deregibus, V. Cantaluppi, R. Calogero et al., “Endothelial progenitor cell—derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA,” Blood, vol. 110, no. 7, pp. 2440–2448, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. 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
  11. A. Bobrie, M. Colombo, G. Raposo, and C. Théry, “Exosome secretion: molecular mechanisms and roles in immune responses,” Traffic, vol. 12, no. 12, pp. 1659–1668, 2011. View at Publisher · View at Google Scholar · View at Scopus
  12. S. Mathivanan, H. Ji, and R. J. Simpson, “Exosomes: extracellular organelles important in intercellular communication,” Journal of Proteomics, vol. 73, no. 10, pp. 1907–1920, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. 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
  14. A. Piccin, W. G. Murphy, and O. P. Smith, “Circulating microparticles: pathophysiology and clinical implications,” Blood Reviews, vol. 21, no. 3, pp. 157–171, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. D. M. Smalley, N. E. Sheman, K. Nelson, and D. Theodorescu, “Isolation and identification of potential urinary microparticle biomarkers of bladder cancer,” Journal of Proteome Research, vol. 7, no. 5, pp. 2088–2096, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. 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
  17. H. Peinado, M. Alečković, S. Lavotshkin et al., “Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET,” Nature Medicine, vol. 18, no. 6, pp. 883–891, 2012. View at Publisher · View at Google Scholar · View at Scopus
  18. H. Shao, J. Chung, L. Balaj et al., “Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy,” Nature Medicine, vol. 18, no. 12, pp. 1835–1840, 2012. View at Publisher · View at Google Scholar · View at Scopus
  19. Y. Yoshioka, N. Kosaka, Y. Konishi et al., “Ultra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen,” Nature Communications, vol. 5, article 3591, 2014. View at Google Scholar
  20. H. Im, H. Shao, Y. I. Park et al., “Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor,” Nature Biotechnology, vol. 32, no. 5, pp. 490–495, 2014. View at Publisher · View at Google Scholar · View at Scopus
  21. R. Jaenisch and A. Bird, “Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals,” Nature Genetics, vol. 33, pp. 245–254, 2003. View at Publisher · View at Google Scholar · View at Scopus
  22. Y. Lee, S. El Andaloussi, and M. J. A. Wood, “Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy,” Human Molecular Genetics, vol. 21, no. 1, Article ID dds317, pp. R125–R134, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. S. El Andaloussi, I. Mäger, X. O. Breakefield, and M. J. A. Wood, “Extracellular vesicles: biology and emerging therapeutic opportunities,” Nature Reviews Drug Discovery, vol. 12, no. 5, pp. 347–357, 2013. View at Publisher · View at Google Scholar · View at Scopus
  24. A. Sharma, “Bioinformatic analysis revealing association of exosomal mRNAs and proteins in epigenetic inheritance,” Journal of Theoretical Biology, vol. 357, pp. 143–149, 2014. View at Publisher · View at Google Scholar · View at Scopus
  25. 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 · View at Scopus
  26. G. Rabinowits, C. Gerçel-Taylor, J. M. Day, D. D. Taylor, and G. H. Kloecker, “Exosomal microRNA: a diagnostic marker for lung cancer,” Clinical Lung Cancer, vol. 10, no. 1, pp. 42–46, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. F. Chik, M. Szyf, and S. A. Rabbani, “Role of epigenetics in cancer initiation and progression,” Advances in Experimental Medicine and Biology, vol. 720, pp. 91–104, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. S. D. Fouse and J. F. Costello, “Epigenetics of neurological cancers,” Future Oncology, vol. 5, no. 10, pp. 1615–1629, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. O. Kovalchuk, V. P. Tryndyak, B. Montgomery et al., “Estrogen-induced rat breast carcinogenesis is characterized by alterations in DNA methylation, histone modifications and aberrant microRNA expression,” Cell Cycle, vol. 6, no. 16, pp. 2010–2018, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. K. D. Robertson, E. Uzvolgyi, G. Liang et al., “The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors,” Nucleic Acids Research, vol. 27, no. 11, pp. 2291–2298, 1999. View at Publisher · View at Google Scholar · View at Scopus
  31. C. Popp, W. Dean, S. Feng et al., “Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency,” Nature, vol. 463, no. 7284, pp. 1101–1105, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. L. Shen, H. Wu, D. Diep et al., “Genome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics,” Cell, vol. 153, no. 3, pp. 692–706, 2013. View at Publisher · View at Google Scholar · View at Scopus
  33. 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
  34. X. Zhu, Y. You, Q. Li et al., “BCR-ABL1-positive microvesicles transform normal hematopoietic transplants through genomic instability: Implications for donor cell leukemia,” Leukemia, vol. 28, no. 8, pp. 1666–1675, 2014. View at Publisher · View at Google Scholar · View at Scopus
  35. Y. Yoshioka, Y. Konishi, N. Kosaka, T. Katsuda, T. Kato, and T. Ochiya, “Comparative marker analysis of extracellular vesicles in different human cancer types,” Journal of Extracellular Vesicles, vol. 2, 2013. View at Publisher · View at Google Scholar
  36. C. Kahlert, S. A. Melo, A. Protopopov et al., “Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer,” The Journal of Biological Chemistry, vol. 289, no. 7, pp. 3869–3875, 2014. View at Publisher · View at Google Scholar · View at Scopus
  37. Y. Yoshida, H. Yamamoto, R. Morita et al., “Detection of DNA methylation of gastric juice-derived exosomes in gastric cancer,” Integrative Molecular Medicine, 2014. View at Publisher · View at Google Scholar
  38. Y. Watanabe, H. S. Kim, R. J. Castoro et al., “Sensitive and specific detection of early gastric cancer with DNA methylation analysis of gastric washes,” Gastroenterology, vol. 136, no. 7, pp. 2149–2158, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. Oishi, Y. Watanabe, Y. Yoshida et al., “Hypermethylation of Sox17 gene is useful as a molecular diagnostic application in early gastric cancer,” Tumor Biology, vol. 33, no. 2, pp. 383–393, 2012. View at Publisher · View at Google Scholar · View at Scopus
  40. D. Vigetti, M. Viola, E. Karousou et al., “Epigenetics in extracellular matrix remodeling and hyaluronan metabolism,” FEBS Journal, vol. 281, no. 22, pp. 4980–4992, 2014. View at Publisher · View at Google Scholar · View at Scopus
  41. S. U. Kass and A. P. Wolffe, “DNA methylation, nucleosomes and the inheritance of chromatin structure and function,” Novartis Foundation Symposium, vol. 214, pp. 22–50, 1998. View at Google Scholar · View at Scopus
  42. M. Verma and S. Srivastava, “Epigenetics in cancer: implications for early detection and prevention,” The Lancet Oncology, vol. 3, no. 12, pp. 755–763, 2002. View at Publisher · View at Google Scholar · View at Scopus
  43. A. Munshi, G. Shafi, N. Aliya, and A. Jyothy, “Histone modifications dictate specific biological readouts,” Journal of Genetics and Genomics, vol. 36, no. 2, pp. 75–88, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. K. K. Lee and J. L. Workman, “Histone acetyltransferase complexes: one size doesn't fit all,” Nature Reviews Molecular Cell Biology, vol. 8, no. 4, pp. 284–295, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. B. Li, M. Carey, and J. L. Workman, “The role of chromatin during transcription,” Cell, vol. 128, no. 4, pp. 707–719, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. H. Hou and H. Yu, “Structural insights into histone lysine demethylation,” Current Opinion in Structural Biology, vol. 20, no. 6, pp. 739–748, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. P. Gallinari, S. Di Marco, P. Jones, M. Pallaoro, and C. Steinkühler, “HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics,” Cell Research, vol. 17, no. 3, pp. 195–211, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. M.-H. Kuo and C. D. Allis, “Roles of histone acetyltransferases and deacetylases in gene regulation,” BioEssays, vol. 20, no. 8, pp. 615–626, 1998. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Grunstein, “Histone acetylation in chromatin structure and transcription,” Nature, vol. 389, no. 6649, pp. 349–352, 1997. View at Publisher · View at Google Scholar · View at Scopus
  50. A. Sharma, “Novel transcriptome data analysis implicates circulating microRNAs in epigenetic inheritance in mammals,” Gene, vol. 538, no. 2, pp. 366–372, 2014. View at Publisher · View at Google Scholar · View at Scopus
  51. S. Mathivanan, C. J. Fahner, G. E. Reid, and R. J. Simpson, “ExoCarta 2012: database of exosomal proteins, RNA and lipids,” Nucleic Acids Research, vol. 40, no. 1, pp. D1241–D1244, 2012. View at Publisher · View at Google Scholar · View at Scopus
  52. R. J. Simpson, H. Kalra, and S. Mathivanan, “ExoCarta as a resource for exosomal research,” Journal of Extracellular Vesicles, vol. 1, Article ID 18374, 2012. View at Google Scholar
  53. G. Schiera, C. M. Di Liegro, P. Saladino et al., “Oligodendroglioma cells synthesize the differentiation-specific linker histone H1° and release it into the extracellular environment through shed vesicles,” International Journal of Oncology, vol. 43, no. 6, pp. 1771–1776, 2013. View at Publisher · View at Google Scholar · View at Scopus
  54. A. Izzo, K. Kamieniarz, and R. Schneider, “The histone H1 family: specific members, specific functions?” Biological Chemistry, vol. 389, no. 4, pp. 333–343, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. W. F. Marzluff, P. Gongidi, K. R. Woods, J. Jin, and L. J. Maltais, “The human and mouse replication-dependent histone genes,” Genomics, vol. 80, no. 5, pp. 487–498, 2002. View at Publisher · View at Google Scholar · View at Scopus
  56. N. Happel and D. Doenecke, “Histone H1 and its isoforms: contribution to chromatin structure and function,” Gene, vol. 431, no. 1-2, pp. 1–12, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. A. Kowalski and J. Pałyga, “Linker histone subtypes and their allelic variants,” Cell Biology International, vol. 36, no. 11, pp. 981–996, 2012. View at Publisher · View at Google Scholar · View at Scopus
  58. J. Zlatanova and D. Doenecke, “Histone H1 zero: a major player in cell differentiation?” The FASEB Journal, vol. 8, no. 15, pp. 1260–1268, 1994. View at Google Scholar · View at Scopus
  59. D. I. Gabrilovich, P. Cheng, Y. Fan et al., “H1 histone and differentiation of dendritic cells. A molecular target for tumor-derived factors,” Journal of Leukocyte Biology, vol. 72, no. 2, pp. 285–296, 2002. View at Google Scholar · View at Scopus
  60. C. H. Lawrie, S. Gal, H. M. Dunlop et al., “Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma,” British Journal of Haematology, vol. 141, no. 5, pp. 672–675, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. P. S. Mitchell, R. K. Parkin, E. M. Kroh et al., “Circulating microRNAs as stable blood-based markers for cancer detection,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 30, pp. 10513–10518, 2008. View at Publisher · View at Google Scholar
  62. R. Ma, T. Jiang, and X. Kang, “Circulating microRNAs in cancer: origin, function and application,” Journal of Experimental and Clinical Cancer Research, vol. 31, no. 1, article 38, 2012. View at Publisher · View at Google Scholar · View at Scopus
  63. V. Ambros, “The functions of animal microRNAs,” Nature, vol. 431, no. 7006, pp. 350–355, 2004. View at Publisher · View at Google Scholar · View at Scopus
  64. D. P. Bartel, “MicroRNAs: genomics, biogenesis, mechanism, and function,” Cell, vol. 116, no. 2, pp. 281–297, 2004. View at Publisher · View at Google Scholar · View at Scopus
  65. X. Huang, T. Yuan, M. Tschannen et al., “Characterization of human plasma-derived exosomal RNAs by deep sequencing,” BMC Genomics, vol. 14, no. 1, article 319, 2013. View at Publisher · View at Google Scholar · View at Scopus
  66. D. M. Pegtel, K. Cosmopoulos, D. A. Thorley-Lawson et al., “Functional delivery of viral miRNAs via exosomes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 14, pp. 6328–6333, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. D. J. Gibbings, C. Ciaudo, M. Erhardt, and O. Voinnet, “Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity,” Nature Cell Biology, vol. 11, no. 9, pp. 1143–1149, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. N. Kosaka, H. Iguchi, Y. Yoshioka, F. Takeshita, Y. Matsuki, and T. Ochiya, “Secretory mechanisms and intercellular transfer of microRNAs in living cells,” Journal of Biological Chemistry, vol. 285, no. 23, pp. 17442–17452, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. 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, no. 5, pp. 447–450, 2014. View at Publisher · View at Google Scholar
  70. G. Rappa, J. Mercapide, F. Anzanello et al., “Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells,” Experimental Cell Research, vol. 319, no. 6, pp. 810–819, 2013. View at Publisher · View at Google Scholar · View at Scopus
  71. A. Lorico, J. Mercapide, and G. Rappa, “Prominin-1 (CD133) and metastatic melanoma: current knowledge and therapeutic perspectives,” Advances in Experimental Medicine and Biology, vol. 777, pp. 197–211, 2013. View at Publisher · View at Google Scholar · View at Scopus
  72. G. Rappa, O. Fodstad, and A. Lorico, “The stem cell-associated antigen CD133 (Prominin-1) is a molecular therapeutic target for metastatic melanoma,” Stem Cells, vol. 26, no. 12, pp. 3008–3017, 2008. View at Publisher · View at Google Scholar · View at Scopus
  73. G. Rappa, J. Mercapide, F. Anzanello, R. M. Pope, and A. Lorico, “Biochemical and biological characterization of exosomes containing prominin-1/CD133,” Molecular Cancer, vol. 12, no. 1, article 62, 2013. View at Publisher · View at Google Scholar · View at Scopus
  74. 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
  75. S. Rana, K. Malinowska, and M. Zöller, “Exosomal tumor microRNA modulates premetastatic organ cells,” Neoplasia, vol. 15, no. 3, pp. 281–295, 2013. View at Publisher · View at Google Scholar · View at Scopus
  76. 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 · View at Scopus
  77. S. Taverna, V. Amodeo, L. Saieva et al., “Exosomal shuttling of miR-126 in endothelial cells modulates adhesive and migratory abilities of chronic myelogenous leukemia cells,” Molecular Cancer, vol. 13, no. 1, article 169, 2014. View at Publisher · View at Google Scholar · View at Scopus
  78. N. Tominaga, N. Kosaka, M. Ono et al., “Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier,” Nature Communications, vol. 6, p. 6716, 2015. View at Publisher · View at Google Scholar
  79. W. Zhou, M. Y. Fong, Y. Min et al., “Cancer-Secreted miR-105 destroys vascular endothelial barriers to promote metastasis,” Cancer Cell, vol. 25, no. 4, pp. 501–515, 2014. View at Publisher · View at Google Scholar · View at Scopus
  80. M. Ono, N. Kosaka, N. Tominaga et al., “Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells,” Science Signaling, vol. 7, no. 332, article ra63, 2014. View at Publisher · View at Google Scholar · View at Scopus
  81. N. Kosaka, H. Iguchi, K. Hagiwara, Y. Yoshioka, F. Takeshita, and T. Ochiya, “Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic micrornas regulate cancer cell metastasis,” The Journal of Biological Chemistry, vol. 288, no. 15, pp. 10849–10859, 2013. View at Publisher · View at Google Scholar · View at Scopus
  82. T. Kogure, W.-L. Lin, I. K. Yan, C. Braconi, and T. Patel, “Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth,” Hepatology, vol. 54, no. 4, pp. 1237–1248, 2011. View at Publisher · View at Google Scholar · View at Scopus
  83. S.-I. Ohno, M. Takanashi, K. Sudo et al., “Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells,” Molecular Therapy, vol. 21, no. 1, pp. 185–191, 2013. View at Publisher · View at Google Scholar · View at Scopus
  84. J. M. Perkel, “Visiting ‘noncodarnia’,” BioTechniques, vol. 54, no. 6, pp. 301–304, 2013. View at Publisher · View at Google Scholar · View at Scopus
  85. I. Grammatikakis, A. C. Panda, K. Abdelmohsen, and M. Gorospe, “Long noncoding RNAs (lncRNAs) and the molecular hallmarks of aging,” Aging, vol. 6, no. 12, pp. 992–1009, 2014. View at Google Scholar · View at Scopus
  86. U. Gezer, E. Özgür, M. Cetinkaya, M. Isin, and N. Dalay, “Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes,” Cell Biology International, vol. 38, no. 9, pp. 1076–1079, 2014. View at Publisher · View at Google Scholar
  87. T. Kogure, I. K. Yan, W.-L. Lin, and T. Patel, “Extracellular vesicle-mediated transfer of a novel long noncoding RNA TUC339: a mechanism of intercellular signaling in human hepatocellular cancer,” Genes & Cancer, vol. 4, no. 7-8, pp. 261–272, 2013. View at Publisher · View at Google Scholar · View at Scopus
  88. C. Braconi, N. Valeri, T. Kogure et al., “Expression and functional role of a transcribed noncoding RNA with an ultraconserved element in hepatocellular carcinoma,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 2, pp. 786–791, 2011. View at Publisher · View at Google Scholar · View at Scopus
  89. K. Takahashi, I. K. Yan, T. Kogure, H. Haga, and T. Patel, “Extracellular vesicle-mediated transfer of long non-coding RNA ROR modulates chemosensitivity in human hepatocellular cancer,” FEBS Open Bio, vol. 4, pp. 458–467, 2014. View at Publisher · View at Google Scholar · View at Scopus
  90. L. H. Schmidt, T. Spieker, S. Koschmieder et al., “The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth,” Journal of Thoracic Oncology, vol. 6, no. 12, pp. 1984–1992, 2011. View at Publisher · View at Google Scholar · View at Scopus
  91. R. Lin, S. Maeda, C. Liu, M. Karin, and T. S. Edgington, “A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas,” Oncogene, vol. 26, no. 6, pp. 851–858, 2007. View at Publisher · View at Google Scholar · View at Scopus
  92. D. G. Weber, G. Johnen, S. Casjens et al., “Evaluation of long noncoding RNA MALAT1 as a candidate blood-based biomarker for the diagnosis of non-small cell lung cancer,” BMC Research Notes, vol. 6, no. 1, article 518, 2013. View at Publisher · View at Google Scholar · View at Scopus
  93. S. Raimondo, L. Saieva, C. Corrado et al., “Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism,” Cell Communication and Signaling, vol. 13, no. 1, article 8, 2015. View at Publisher · View at Google Scholar
  94. C. Corrado, S. Raimondo, A. Chiesi, F. Ciccia, G. De Leo, and R. Alessandro, “Exosomes as intercellular signaling organelles involved in health and disease: basic science and clinical applications,” International Journal of Molecular Sciences, vol. 14, no. 3, pp. 5338–5366, 2013. View at Publisher · View at Google Scholar · View at Scopus