Exosomal microRNA Biomarkers: Emerging Frontiers in Colorectal and Other Human Cancers

Expert Review of Molecular Diagnostics

Volumn 16, Issue 5, 2016, Pages 553-567

  Tovar Camargo, Oscar A ^a   Toden, Shusuke ^a   Goel, Ajay ^a  

^a BAYLOR RESEARCH INSTITUTE   (United States)

Author keywords

biomarker; cancer; colorectal cancer; diagnosis; epigenetic; Exosomes; microRNA

Indexed keywords

MICRORNA; NUCLEIC ACID; PROTEIN; TUMOR MARKER; ANNEXIN; CALCIUM BINDING PROTEIN; CELL CYCLE PROTEIN; DNA BINDING PROTEIN; ESCRT PROTEIN; LEUKOCYTE ANTIGEN; PDCD6IP PROTEIN, HUMAN; TRANSCRIPTION FACTOR; TUMOR PROTEIN; TUMOR SUSCEPTIBILITY GENE 101 PROTEIN;

BIOGENESIS; BLOOD SAMPLING; CANCER CELL; CANCER CELL LINE; CANCER GROWTH; COLORECTAL CANCER; ENDOCYTOSIS; EPIGENETICS; EXOSOME; GENE EXPRESSION PROFILING; HOST CELL; HUMAN; NONHUMAN; PROTEIN EXPRESSION; REVIEW; BLOOD; CHEMISTRY; COLORECTAL NEOPLASMS; GENE EXPRESSION REGULATION; GENETICS; PATHOLOGY;

ANNEXINS; ANTIGENS, CD; BIOMARKERS, TUMOR; CALCIUM-BINDING PROTEINS; CELL CYCLE PROTEINS; COLORECTAL NEOPLASMS; DNA-BINDING PROTEINS; ENDOSOMAL SORTING COMPLEXES REQUIRED FOR TRANSPORT; EXOSOMES; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MICRORNAS; NEOPLASM PROTEINS; TRANSCRIPTION FACTORS;

EID: 84961214442     PISSN: 14737159     EISSN: 17448352     Source Type: Journal    
DOI: 10.1586/14737159.2016.1156535     Document Type: Review

References (170)

1. Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin. 2014;64(2):104-117.
2. Singh H, Nugent Z, Demers AA, et al. The reduction in colorectal cancer mortality after colonoscopy varies by site of the cancer. Gastroenterology. 2010;139(4):1128-1137.
3. Kahi CJ, Imperiale TF, Juliar BE, et al. Effect of screening colonoscopy on colorectal cancer incidence and mortality. Clin Gastroenterol Hepatol: Official Clin Pract J Am Gastroenterol Assoc. 2009;7(7):770-775. quiz 711.
4. Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Colorectal Cancer Study G. Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med. 2004;351 (26):2704-2714.
5. Van Rossum LG, Van Rijn AF, Van Oijen MG, et al. False negative fecal occult blood tests due to delayed sample return in colorectal cancer screening. Int J Cancer. 2009;125(4):746-750.
6. Osborne J, Wilson C, Moore V, et al. Sample preference for colorectal cancer screening tests: blood or stool? Open J Prev Med. 2012;2:326-331.
7. Gyorgy B, Szabo TG, Pasztoi M, et al. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci. 2011;68(16):2667-2688.
8. Yanez-Mo M, Siljander PR, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066.
9. Keller S, Rupp C, Stoeck A, et al. CD24 is a marker of exosomes secreted into urine and amniotic fluid. Kidney Int. 2007;72(9):1095-1102.
10. Azmi AS, Bao B, Sarkar FH. Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev. 2013;32(3-4):623-642.
11. Melo SA, Luecke LB, Kahlert C, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature. 2015;523 (7559):177-182.
12. De Jong OG, Verhaar MC, Chen Y, et al. Cellular stress conditions are reflected in the protein and RNA content of endothelial cell-derived exosomes. J Extracell Vesicles. 2012;1. Article ID 18396.
13. Witwer KW, Buzas EI, Bemis LT, et al. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles. 2013;2. Article ID 20360.
14. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11(9):597-610.
15. Schwarzenbach H, Nishida N, Calin GA, et al. Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol. 2014;11(3):145-156.
16. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281-297.
17. Okugawa Y, Toiyama Y, Goel A. An update on microRNAs as colorectal cancer biomarkers: where are we and what's next? Expert Rev Mol Diagn. 2014;14(8):999-1021.
18. Yamada A, Horimatsu T, Okugawa Y, et al. Serum miR-21, miR-29a and miR-125b are promising biomarkers for the early detection of colorectal neoplasia. Clin Cancer Res: Official J Am Assoc Cancer Res. 2015;21(18):4234-4242.
19. Toiyama Y, Takahashi M, Hur K, et al. Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer. J Natl Cancer Inst. 2013;105(12):849-859.
20. Hewitson P, Glasziou P, Watson E, et al. Cochrane systematic review of colorectal cancer screening using the fecal occult blood test (hemoccult): an update. Am J Gastroenterol. 2008;103(6):1541-1549.
21. Guittet L, Bouvier V, Mariotte N, et al. Comparison of a guaiac based and an immunochemical faecal occult blood test in screening for colorectal cancer in a general average risk population. Gut. 2007;56(2):210-214.
22. Quintero E, Castells A, Bujanda L, et al. Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. N Engl J Med. 2012;366(8):697-706.
23. Scheel C, Eaton EN, Li SH, et al. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell. 2011;145(6):926-940.
24. Mar-Aguilar F, Rodriguez-Padilla C, Resendez-Perez D. Use of serum-circulating miRNA profiling for the identification of breast cancer biomarkers. Methods Mol Biol. 2014;1165:71-80.
25. Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med. 2004;350(22):2239-2246.
26. Chute JP, Taylor E, Williams J, et al. A metabolic study of patients with lung cancer and hyponatremia of malignancy. Clin Cancer Res: Official J Am Assoc Cancer Res. 2006;12(3 Pt 1):888-896.
27. Gold P, Freedman SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med. 1965;122(3):467-481.
28. Gold P, Freedman SO. Demonstration of tumor-specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques. J Exp Med. 1965;121:439-462.
29. Moertel CG, Fleming TR, Macdonald JS, et al. An evaluation of the carcinoembryonic antigen (CEA) test for monitoring patients with resected colon cancer. JAMA. 1993;270(8):943-947.
30. Patriarca C, Macchi RM, Marschner AK, et al. Epithelial cell adhesion molecule expression (CD326) in cancer: a short review. Cancer Treat Rev. 2012;38(1):68-75.
31. Went PT, Lugli A, Meier S, et al. Frequent EpCam protein expression in human carcinomas. Hum Pathol. 2004;35(1):122-128.
32. Grutzmann R, Molnar B, Pilarsky C, et al. Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay. Plos One. 2008;3(11):e3759.
33. Ebert MP, Model F, Mooney S, et al. Aristaless-like homeobox-4 gene methylation is a potential marker for colorectal adenocarcinomas. Gastroenterology. 2006;131(5):1418-1430.
34. Levenson VV. DNA methylation as a universal biomarker. Expert Rev Mol Diagn. 2010;10(4):481-488.
35. Summers T, Langan RC, Nissan A, et al. Serum-based DNA methylation biomarkers in colorectal cancer: potential for screening and early detection. J Cancer. 2013;4(3):210-216.
36. Simpson RJ, Jensen SS, Lim JW. Proteomic profiling of exosomes: current perspectives. Proteomics. 2008;8(19):4083-4099.
37. Van Niel G, Raposo G, Candalh C, et al. Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology. 2001;121(2):337-349.
38. Wolfers J, Lozier A, Raposo G, et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med. 2001;7(3):297-303.
39. Clayton A, Mitchell JP, Court J, et al. Human tumor-derived exosomes down-modulate NKG2D expression. J Immunology. 2008;180(11):7249-7258.
40. Blanchard N, Lankar D, Faure F, et al. TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/ zeta complex. J Immunology. 2002;168(7):3235-3241.
41. Caby MP, Lankar D, Vincendeau-Scherrer C, et al. Exosomal-like vesicles are present in human blood plasma. Int Immunol. 2005;17(7):879-887.
42. Ogawa Y, Miura Y, Harazono A, et al. Proteomic analysis of two types of exosomes in human whole saliva. Biol Pharm Bull. 2011;34 (1):13-23.
43. Asea A, Jean-Pierre C, Kaur P, et al. Heat shock protein-containing exosomes in mid-trimester amniotic fluids. J Reprod Immunol. 2008;79(1):12-17.
44. Bretz NP, Ridinger J, Rupp AK, et al. Body fluid exosomes promote secretion of inflammatory cytokines in monocytic cells via Toll-like receptor signaling. J Biol Chem. 2013;288(51):36691-36702.
45. Admyre C, Johansson SM, Qazi KR, et al. Exosomes with immune modulatory features are present in human breast milk. J Immunology. 2007;179(3):1969-1978.
46. Vella LJ, Sharples RA, Lawson VA, et al. Packaging of prions into exosomes is associated with a novel pathway of PrP processing. J Pathol. 2007;211(5):582-590.
47. Trams EG, Lauter CJ, Salem N Jr., et al. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta. 1981;645(1):63-70.
48. Johnstone RM, Adam M, Hammond JR, et al. Vesicle formation during reticulocyte maturation. Assoc Plasma Membrane Activit Released Vesicles (Exosomes). J Biol Chem. 1987;262(19):9412-9420.
49. Tauro BJ, Greening DW, Mathias RA, et al. Two distinct populations of exosomes are released from LIM1863 colon carcinoma cellderived organoids. Mol Cell Proteomics. 2013;12(3):587-598.
50. Mathivanan S, Lim JW, Tauro BJ, et al. Proteomics analysis of A33 immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature. Mol Cell Proteomics. 2010;9(2):197-208.
51. Xu R, Greening DW, Rai A, et al. Highly-purified exosomes and shed microvesicles isolated from the human colon cancer cell line LIM1863 by sequential centrifugal ultrafiltration are biochemically and functionally distinct. Methods. 2015;87:11-25.
52. Escola JM, Kleijmeer MJ, Stoorvogel W, et al. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem. 1998;273(32):20121-20127.
53. Bukong TN, Momen-Heravi F, Kodys K, et al. Exosomes from hepatitis C infected patients transmit HCV infection and contain replication competent viral RNA in complex with Ago2-miR122-HSP90. PLoS Pathog. 2014;10(10):e1004424.
54. De Gassart A, Geminard C, Fevrier B, et al. Lipid raft-associated protein sorting in exosomes. Blood. 2003;102(13):4336-4344.
55. Calzolari A, Raggi C, Deaglio S, et al. TfR2 localizes in lipid raft domains and is released in exosomes to activate signal transduction along the MAPK pathway. J Cell Sci. 2006;119(Pt 21):4486-4498.
56. Wubbolts R, Leckie RS, Veenhuizen PT, et al. Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J Biol Chem. 2003;278(13):10963-10972.
57. Piper RC, Katzmann DJ. Biogenesis and function of multivesicular bodies. Annu Rev Cell Dev Biol. 2007;23:519-547.
58. Savina A, Fader CM, Damiani MT, et al. Rab11 promotes docking and fusion of multivesicular bodies in a calcium-dependent manner. Traffic. 2005;6(2):131-143.
59. Matsuo H, Chevallier J, Mayran N, et al. Role of LBPA and Alix in multivesicular liposome formation and endosome organization. Science. 2004;303(5657):531-534.
60. Roucourt B, Meeussen S, Bao J, et al. Heparanase activates the syndecan-syntenin-ALIX exosome pathway. Cell Res. 2015;25 (4):412-428.
61. Thompson CA, Purushothaman A, Ramani VC, et al. Heparanase regulates secretion, composition, and function of tumor cellderived exosomes. J Biol Chem. 2013;288(14):10093-10099.
62. Baietti MF, Zhang Z, Mortier E, et al. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol. 2012;14(7):677-685.
63. Mulcahy LA, Pink RC, Carter DR. Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles. 2014;3. Article ID 24641.
64. Henne WM, Buchkovich NJ, Emr SD. The ESCRT pathway. Dev Cell. 2011;21(1):77-91.
65. Katzmann DJ, Babst M, Emr SD. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell. 2001;106 (2):145-155.
66. Van Niel G, Wubbolts R, Ten Broeke T, et al. Dendritic cells regulate exposure of MHC class II at their plasma membrane by oligoubiquitination. Immunity. 2006;25(6):885-894.
67. Wollert T, Hurley JH. Molecular mechanism of multivesicular body biogenesis by ESCRT complexes. Nature. 2010;464 (7290):864-869.
68. Raiborg C, Stenmark H. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature. 2009;458(7237):445-452.
69. Schmidt O, Teis D. The ESCRT machinery. Curr Biol: CB. 2012;22(4): R116-120.
70. Castro-Gomes T, Koushik AB, Andrews NW. ESCRT: nipping the wound in the bud? Trends Biochem Sci. 2014;39(7):307-309.
71. Trajkovic K, Hsu C, Chiantia S, et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008;319 (5867):1244-1247.
72. Kosaka N, Iguchi H, Hagiwara K, et al. Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic microRNAs regulate cancer cell metastasis. J Biol Chem. 2013;288(15):10849-10859.
73. Hoshino D, Kirkbride KC, Costello K, et al. Exosome secretion is enhanced by invadopodia and drives invasive behavior. Cell Rep. 2013;5(5):1159-1168.
74. Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. 2008;110(1):13-21.
75. Szajnik M, Derbis M, Lach M, et al. Exosomes in plasma of patients with ovarian carcinoma: potential biomarkers of tumor progression and response to therapy. Gynecol Obstetrics. 2013;Suppl 4(3). Article ID 003.
76. Federici C, Petrucci F, Caimi S, et al. Exosome release and low pH belong to a framework of resistance of human melanoma cells to cisplatin. Plos One. 2014;9(2):e88193.
77. Parolini I, Federici C, Raggi C, et al. Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem. 2009;284 (49):34211-34222.
78. Ge Q, Zhou Y, Lu J, et al. miRNA in plasma exosome is stable under different storage conditions. Molecules. 2014;19(2):1568-1575.
79. Kalra H, Adda CG, Liem M, et al. Comparative proteomics evaluation of plasma exosome isolation techniques and assessment of the stability of exosomes in normal human blood plasma. Proteomics. 2013;13(22):3354-3364.
80. Zhou W, Fong MY, Min Y, et al. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell. 2014;25(4):501-515.
81. Kucharzewska P, Christianson HC, Welch JE, et al. Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development. Proc Natl Acad Sci U S A. 2013;110(18):7312-7317.
82. Ekstrom EJ, Bergenfelz C, Von Bulow V, et al. WNT5A induces release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells. Mol Cancer. 2014;13:88.
83. Skog J, Wurdinger T, Van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10(12):1470-1476.
84. Ji H, Greening DW, Barnes TW, et al. Proteome profiling of exosomes derived from human primary and metastatic colorectal cancer cells reveal differential expression of key metastatic factors and signal transduction components. Proteomics. 2013;13(10-11):1672-1686.
85. Al-Nedawi K, Meehan B, Micallef J, et al. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol. 2008;10(5):619-624.
86. Lokody I. Genetics: exosomally derived miR-105 destroys tight junctions. Nat Rev Cancer. 2014;14(6):386-387.
87. Grange C, Tapparo M, Collino F, et al. Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche. Cancer Res. 2011;71(15):5346-5356.
88. Tadokoro H, Umezu T, Ohyashiki K, et al. Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells. J Biol Chem. 2013;288(48):34343-34351.
89. Rana S, Malinowska K, Zoller M. Exosomal tumor microRNA modulates premetastatic organ cells. Neoplasia. 2013;15(3):281-295.
90. Luga V, Zhang L, Viloria-Petit AM, et al. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell. 2012;151(7):1542-1556.
91. Webber J, Steadman R, Mason MD, et al. Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer Res. 2010;70 (23):9621-9630.
92. Roma-Rodrigues C, Fernandes AR, Baptista PV. Exosome in tumour microenvironment: overview of the crosstalk between normal and cancer cells. Biomed Res Int. 2014;2014:179486.
93. Hood JL, San RS, Wickline SA. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res. 2011;71(11):3792-3801.
94. Boelens MC, Wu TJ, Nabet BY, et al. Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. Cell. 2014;159(3):499-513.
95. Peinado H, Aleckovic M, Lavotshkin S, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med. 2012;18(6):883-891.
96. Bobrie A, Krumeich S, Reyal F, et al. Rab27a supports exosomedependent and -independent mechanisms that modify the tumor microenvironment and can promote tumor progression. Cancer Res. 2012;72(19):4920-4930.
97. Chiba M, Kimura M, Asari S. Exosomes secreted from human colorectal cancer cell lines contain mRNAs, microRNAs and natural antisense RNAs, that can transfer into the human hepatoma HepG2 and lung cancer A549 cell lines. Oncol Rep. 2012;28(5):1551-1558.
98. Hoshino A, Costa-Silva B, Shen TL, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527 (7578):329-335.
99. Tominaga N, Kosaka N, Ono M, et al. Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier. Nat Commun. 2015;3:6716.
100. Ono M, Kosaka N, Tominaga N, et al. Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells. Sci Signal. 2014;7(332): ra63.
101. Zhang H-G, Grizzle WE. Exosomes and cancer: a newly described pathway of immune suppression. Clin Cancer Res: Official J Am Assoc Cancer Res. 2011;17(5):959-964.
102. Pilzer D, Fishelson Z. Mortalin/GRP75 promotes release of membrane vesicles from immune attacked cells and protection from complement-mediated lysis. Int Immunol. 2005;17(9):1239-1248.
103. Aung T, Chapuy B, Vogel D, et al. Exosomal evasion of humoral immunotherapy in aggressive B-cell lymphoma modulated by ATPbinding cassette transporter A3. Proc Natl Acad Sci U S A. 2011;108 (37):15336-15341.
104. Liu T, Mendes DE, Berkman CE. Functional prostate-specific membrane antigen is enriched in exosomes from prostate cancer cells. Int J Oncol. 2014;44(3):918-922.
105. Mhawech-Fauceglia P, Zhang S, Terracciano L, et al. Prostate-specific membrane antigen (PSMA) protein expression in normal and neoplastic tissues and its sensitivity and specificity in prostate adenocarcinoma: an immunohistochemical study using multiple tumour tissue microarray technique. Histopathology. 2007;50 (4):472-483.
106. Oksvold MP, Kullmann A, Forfang L, et al. Expression of B-cell surface antigens in subpopulations of exosomes released from B-cell lymphoma cells. Clin Ther. 2014;36(6):847-862e841.
107. Gengrinovitch S, Berman B, David G, et al. Glypican-1 is a VEGF165 binding proteoglycan that acts as an extracellular chaperone for VEGF165. J Biol Chem. 1999;274(16):10816-10822.
108. Mayor S, Riezman H. Sorting GPI-anchored proteins. Nat Rev Mol Cell Biol. 2004;5(2):110-120.
109. Filmus J, Capurro M, Rast J. Glypicans. Genome Biol. 2008;9(5):224.
110. Cancer Genome Atlas N. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487 (7407):330-337.
111. Qiao D, Meyer K, Friedl A. Glypican-1 stimulates Skp2 autoinduction loop and G1/S transition in endothelial cells. J Biol Chem. 2012;287 (8):5898-5909.
112. Dai S, Wan T, Wang B, et al. More efficient induction of HLAA∗ 0201-restricted and carcinoembryonic antigen (CEA)-specific CTL response by immunization with exosomes prepared from heat-stressed CEA-positive tumor cells. Clin Cancer Res: Official J Am Assoc Cancer Res. 2005;11(20):7554-7563.
113. Peng P, Yan Y, Keng S. Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity. Oncol Rep. 2011;25(3):749-762.
114. Im H, Shao H, Park YI, et al. Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nat Biotechnol. 2014;32(5):490-495.
115. Staubach S, Razawi H, Hanisch FG. Proteomics of MUC1-containing lipid rafts from plasma membranes and exosomes of human breast carcinoma cells MCF-7. Proteomics. 2009;9(10):2820-2835.
116. Ji H, Chen M, Greening DW, et al. Deep sequencing of RNA from three different extracellular vesicle (EV) subtypes released from the human LIM1863 colon cancer cell line uncovers distinct miRNAenrichment signatures. Plos One. 2014;9(10):e110314.
117. Heath JK, White SJ, Johnstone CN, et al. The human A33 antigen is a transmembrane glycoprotein and a novel member of the immunoglobulin superfamily. Proc Natl Acad Sci U S A. 1997;94(2):469-474.
118. Mallegol J, Van Niel G, Lebreton C, et al. T84-intestinal epithelial exosomes bear MHC class II/peptide complexes potentiating antigen presentation by dendritic cells. Gastroenterology. 2007;132 (5):1866-1876.
119. Yoshioka Y, Kosaka N, Konishi Y, et al. Ultra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen. Nat Commun. 2014;5:3591.
120. Greening DW, Kapp EA, Ji H, et al. Colon tumour secretopeptidome: insights into endogenous proteolytic cleavage events in the colon tumour microenvironment. Biochim Biophys Acta. 2013;1834 (11):2396-2407.
121. Silva J, Garcia V, Rodriguez M, et al. Analysis of exosome release and its prognostic value in human colorectal cancer. Genes Chromosomes Cancer. 2012;51(4):409-418.
122. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of posttranscriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet. 2008;9(2):102-114.
123. Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18(10):997-1006.
124. Tiberio P, Callari M, Angeloni V, et al. Challenges in using circulating miRNAs as cancer biomarkers. Biomed Res Int. 2015;2015:731479.
125. Turchinovich A, Weiz L, Langheinz A, et al. Characterization of extracellular circulating microRNA. Nucleic Acids Res. 2011;39 (16):7223-7233.
126. Arroyo JD, Chevillet JR, Kroh EM, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A. 2011;108(12):5003-5008.
127. Gallo A, Tandon M, Alevizos I, et al. The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. Plos One. 2012;7(3):e30679.
128. Melo SA, Sugimoto H, O'Connell JT, et al. Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell. 2014;26(5):707-721.
129. Wei Y, Lai X, Yu S, et al. Exosomal miR-221/222 enhances tamoxifen resistance in recipient ER-positive breast cancer cells. Breast Cancer Res Treat. 2014;147(2):423-431.
130. Mittelbrunn M, Gutierrez-Vazquez C, Villarroya-Beltri C, et al. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun. 2011;2:282.
131. Kruger S, Abd Elmageed ZY, Hawke DH, et al. Molecular characterization of exosome-like vesicles from breast cancer cells. BMC Cancer. 2014;14:44.
132. Hessvik NP, Phuyal S, Brech A, et al. Profiling of microRNAs in exosomes released from PC-3 prostate cancer cells. Biochim Biophys Acta. 2012;1819(11-12):1154-1163.
133. Li Q, Eades G, Yao Y, et al. Characterization of a stem-like subpopulation in basal-like ductal carcinoma in situ (DCIS) lesions. J Biol Chem. 2014;289(3):1303-1312.
134. Singh R, Pochampally R, Watabe K, et al. Exosome-mediated transfer of miR-10b promotes cell invasion in breast cancer. Mol Cancer. 2014;13:256.
135. Zhuang G, Wu X, Jiang Z, et al. Tumour-secreted miR-9 promotes endothelial cell migration and angiogenesis by activating the JAKSTAT pathway. EMBO J. 2012;31(17):3513-3523.
136. Kobayashi M, Salomon C, Tapia J, et al. Ovarian cancer cell invasiveness is associated with discordant exosomal sequestration of Let-7 miRNA and miR-200. J Transl Med. 2014;12:4.
137. Kosaka N, Iguchi H, Yoshioka Y, et al. Competitive interactions of cancer cells and normal cells via secretory microRNAs. J Biol Chem. 2012;287(2):1397-1405.
138. Corcoran C, Rani S, O'Brien K, et al. Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes. Plos One. 2012;7 (12):e50999.
139. Kosaka N, Iguchi H, Yoshioka Y, et al. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem. 2010;285(23):17442-17452.
140. Li CC, Eaton SA, Young PE, et al. Glioma microvesicles carry selectively packaged coding and non-coding RNAs which alter gene expression in recipient cells. RNA Biol. 2013;10(8):1333-1344.
141. Kogure T, Lin WL, Yan IK, et al. Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth. Hepatology. 2011;54(4):1237-1248.
142. Ogata-Kawata H, Izumiya M, Kurioka D, et al. Circulating exosomal microRNAs as biomarkers of colon cancer. Plos One. 2014;9(4): e92921.
143. Yamada N, Nakagawa Y, Tsujimura N, et al. Role of intracellular and extracellular MicroRNA-92a in colorectal cancer. Transl Oncol. 2013;6(4):482-492.
144. Yamada N, Tsujimura N, Kumazaki M, et al. Colorectal cancer cellderived microvesicles containing microRNA-1246 promote angiogenesis by activating Smad 1/5/8 signaling elicited by PML downregulation in endothelial cells. Biochim Biophys Acta. 2014;1839 (11):1256-1272.
145. Senfter D, Holzner S, Kalipciyan M, et al. Loss of miR-200 family in 5-fluorouracil resistant colon cancer drives lymphendothelial invasiveness in vitro. Hum Mol Genet. 2015;24(13):3689-3698.
146. Cha DJ, Franklin JL, Dou Y, et al. KRAS-dependent sorting of miRNA to exosomes. Elife. 2015;4:e07197.
147. Bryant RJ, Pawlowski T, Catto JW, et al. Changes in circulating microRNA levels associated with prostate cancer. Br J Cancer. 2012;106(4):768-774.
148. Que R, Ding G, Chen J, et al. Analysis of serum exosomal microRNAs and clinicopathologic features of patients with pancreatic adenocarcinoma. World J Surg Oncol. 2013;11:219.
149. Sugimachi K, Matsumura T, Hirata H, et al. Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation. Br J Cancer. 2015;112(3):532-538.
150. Nguyen HC, Xie W, Yang M, et al. Expression differences of circulating microRNAs in metastatic castration resistant prostate cancer and low-risk, localized prostate cancer. Prostate. 2013;73(4):346-354.
151. Tanaka Y, Kamohara H, Kinoshita K, et al. Clinical impact of serum exosomal microRNA-21 as a clinical biomarker in human esophageal squamous cell carcinoma. Cancer. 2013;119(6):1159-1167.
152. Rupp AK, Rupp C, Keller S, et al. Loss of EpCAM expression in breast cancer derived serum exosomes: role of proteolytic cleavage. Gynecol Oncol. 2011;122(2):437-446.
153. Mar-Aguilar F, Mendoza-Ramirez JA, Malagon-Santiago I, et al. Serum circulating microRNA profiling for identification of potential breast cancer biomarkers. Dis Markers. 2013;34(3):163-169.
154. Eichelser C, Stuckrath I, Muller V, et al. Increased serum levels of circulating exosomal microRNA-373 in receptor-negative breast cancer patients. Oncotarget. 2014;5(20):9650-9663.
155. Vaksman O, Trope C, Davidson B, et al. Exosome-derived miRNAs and ovarian carcinoma progression. Carcinogenesis. 2014;35 (9):2113-2120.
156. Silva J, Garcia V, Zaballos A, et al. Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival. Eur Respir J. 2011;37(3):617-623.
157. Rabinowits G, Gercel-Taylor C, Day JM, et al. Exosomal microRNA: a diagnostic marker for lung cancer. Clin Lung Cancer. 2009;10(1): 42-46.
158. Matsumura T, Sugimachi K, Iinuma H, et al. Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer. Br J Cancer. 2015;113(2):275-281.
159. Luo X, Burwinkel B, Tao S, et al. MicroRNA signatures: novel biomarker for colorectal cancer? Cancer Epidemiol Biomark Prevent: Publicat Am Assoc Cancer Res, Cosponsor Am Soc Prevent Oncol. 2011;20(7):1272-1286.
160. Iorio MV, Ferracin M, Liu CG, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65 (16):7065-7070.
161. Iorio MV, Visone R, Di Leva G, et al. MicroRNA signatures in human ovarian cancer. Cancer Res. 2007;67(18):8699-8707.
162. Lui WO, Pourmand N, Patterson BK, et al. Patterns of known and novel small RNAs in human cervical cancer. Cancer Res. 2007;67 (13):6031-6043.
163. Seike M, Goto A, Okano T, et al. MiR-21 is an EGFR-regulated antiapoptotic factor in lung cancer in never-smokers. Proc Natl Acad Sci U S A. 2009;106(29):12085-12090.
164. Hu Y, Correa AM, Hoque A, et al. Prognostic significance of differentially expressed miRNAs in esophageal cancer. Int J Cancer. 2011;128(1):132-143.
165. Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005;65(14):6029-6033.
166. Meng F, Henson R, Wehbe-Janek H, et al. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133(2):647-658.
167. Sheedy FJ. Turning 21: induction of miR-21 as a key switch in the inflammatory response. Front Immunol. 2015;6:19.
168. Oom AL, Humphries BA, Yang C. MicroRNAs: novel players in cancer diagnosis and therapies. Biomed Res Int. 2014;2014:959461.
169. Sun G, Cheng YW, Lai L, et al. Signature miRNAs in colorectal cancers were revealed using a bias reduction small RNA deep sequencing protocol. Oncotarget. 2015;7(4):3857-3872.
170. Schee K, Lorenz S, Worren MM, et al. Deep sequencing the MicroRNA transcriptome in colorectal cancer. Plos One. 2013;8(6): e66165.