The role of exosomes contents on genetic and epigenetic alterations of recipient cancer cells

Document Type : Review Article

Authors

1 Department of Biochemistry, Faculty of Basic Science, Payame Noor University, Tehran, Iran

2 Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

3 Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

4 Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Exosomes, as a mediator of cell-to-cell transfer of genetic information, act an important role in intercommunication between tumor cells and their niche including fibroblasts, endothelial cells, adipocytes and monocytes. Several studies have shown that tumor cells can influence their neighboring cells by releasing exosomes. These exosomes provide signaling cues for stimulation, activation, proliferation and differentiation of cells. Exosomes contain mRNAs, microRNAs (miRNA), and proteins that could be transferred to target cells inducing genetic and epigenetic changes. By facilitating the horizontal transfer of bioactive molecules such as proteins, RNAs and microRNAs, they are now thought to have vital roles in tumor invasion and metastases, inflammation, coagulation, and stem cell renewal and expansion. The aim of this review article is to discuss the significance of exosome-mediated intercellular communication within the tumor biology.

Keywords


1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin 2008; 58:71-96.
2. Knudson AG. Two genetic hits (more or less) to cancer. Nat Rev Cancer 2001; 1:157-162.
3. Hannafon BN, Ding WQ. Intercellular communica-tion by exosome-derived microRNAs in cancer. Int J Mol Sci 2013; 14:14240-1469.
4. Shah MY, Calin GA. The mix of two worlds: Non-coding RNAs and hormones. Nucl Acid Ther 2013; 23:2-8.
5. Hosseini HM, Fooladi A, Nourani MR, Ghanezadeh F. The role of exosomes in infectious diseases. Inflamm Allergy Drug Targets 2013; 12:29-37.
6. Ajit SK. Circulating microRNAs as biomarkers, therapeutic targets, and signaling molecules. Sensors 2012; 12:3359-3369.
7. Denzer K, Kleijmeer MJ, Heijnen H, Stoorvogel W, Geuze HJ. Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci 2000; 113:3365-3374.
8. Grange C, Tapparo M, Collino F, Vitillo L, Damasco C, Deregibus MC, et al. Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche. Cancer Res 2011; 71:5346-5356.
9. Kobayashi M, Salomon C, Tapia J, Illanes SE, Mitchell MD, Rice GE. Ovarian cancer cell invasiveness is associated with discordant exosomal sequestration of Let-7 miRNA and miR-200. J Transl Med 2014; 12:4.
10. Minciacchi VR, Freeman MR, Di Vizio D. Extracellular vesicles in cancer: exosomes, microvesicles and the emerging role of large oncosomes. Semin Cell Dev Biol  2015; 40:41-51.
11. Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R, Dvorak P, et al. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 2006; 20:847-856.
12. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9:654-659.
13. Lee TH, Chennakrishnaiah S, Audemard E, Montermini L, Meehan B, Rak J. Oncogenic ras-driven cancer cell vesiculation leads to emission of double-stranded DNA capable of interacting with target cells. Biochem Biophys Res Commun 2014; 451:295-301.
14. Camussi G, Deregibus MC, Bruno S, Grange C, Fonsato V, Tetta C. Exosome/microvesicle-mediated epigenetic reprogramming of cells. Am J Cancer Res 2011; 1:98-110.
15. Di Leva G, Croce CM. miRNA profiling of cancer. Curr Opin Genet Dev 2013; 23:3-11.
16. Samantarrai D, Dash S, Chhetri B, Mallick B. Genomic and epigenomic cross-talks in the regulatory landscape of miRNAs in breast cancer. Mol Cancer Res 2013; 11:315-328.
17. Ohshima K, Inoue K, Fujiwara A, Hatakeyama K, Kanto K, Watanabe Y, et al. Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PloS One 2010; 5:e13247.
18. Rana S, Malinowska K, Zöller M. Exosomal tumor microRNA modulates premetastatic organ cells. Neoplasia 2013; 15:281-IN231.
19. Boon RA, Vickers KC. Intercellular transport of microRNAs. Arterioscler Thromb Vasc Biol 2013; 33:186-192.
20. Ma R, Jiang T, Kang X. Circulating microRNAs in cancer: origin, function and application. J Exp Clin Cancer Res 2012; 31:38.
21. Umezu T, Ohyashiki K, Kuroda M, Ohyashiki J. Leukemia cell to endothelial cell communication via exosomal miRNAs. Oncogene 2012; 32:2747-2755.
22. Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci 2012; 109:E2110-E2116.
23. Zhuang G, Wu X, Jiang Z, Kasman I, Yao J, Guan Y, et al. Tumour‐secreted miR‐9 promotes endothelial cell migration and angiogenesis by activating the JAK‐STAT pathway. TMBO J 2012; 31:3513-3523.
24. Shen G, Lin Y, Yang X, Zhang J, Xu Z, Jia H. MicroRNA-26b inhibits epithelial-mesenchymal transition in hepatocellular carcinoma by targeting USP9X. BMC Cancer 2014; 14:393.
25. Fan X, Chen X, Deng W, Zhong G, Cai Q, Lin T. Up-regulated microRNA-143 in cancer stem cells differentiation promotes prostate cancer cells metastasis by modulating FNDC3B expression. BMC Cancer 2013; 13:61.
26. Lim PK, Bliss SA, Patel SA, Taborga M, Dave MA, Gregory LA, et al. Gap junction–mediated import of microRNA from bone marrow stromal cells can elicit cell cycle quiescence in breast cancer cells. Cancer Res 2011; 71:1550-1560.
27. Rak J. Microparticles in cancer. InSeminars in thrombosis and hemostasis 2010; 36:888-906.
28. Beach A, Zhang HG, Ratajczak MZ, Kakar SS. Exosomes: an overview of biogenesis, composition and role in ovarian cancer. J Ovarian Res 2014; 7:14.
29. Hood JL, San RS, Wickline SA. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res 2011; 71:3792-3801.
30. Sheldon H, Heikamp E, Turley H, Dragovic R, Thomas P, Oon CE, et al. New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes. Blood 2010; 116:2385-2394.
31. Nazarenko I, Rana S, Baumann A, McAlear J, Hellwig A, Trendelenburg M, et al. Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation. Cancer Res 2010; 70:1668-1678.
32. Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 2008; 10:1470-1476.
33. Kang SY LJU, Kim KW. Biosorption of Cr(III) and Cr(VI) onto the cell surface of Pseudomonas aeruginosa. Biochem Eng J 2007; 36:54-58.
34. Hong BS, Cho JH, Kim H, Choi EJ, Rho S, Kim J, et al. Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells. BMC Genomics 2009; 10:556.
35. Katoh M. Therapeutics targeting angiogenesis: Genetics and epigenetics, extracellular miRNAs and signaling networks (Review). Int J Mol Med 2013; 32:763-767.
36. Wysoczynski M, Ratajczak MZ. Lung cancer secreted microvesicles: underappreciated modulators of microenvironment in expanding tumors. Int J Cancer 2009; 125:1595-1603.
37. Henderson MC, Azorsa DO. The genomic and proteomic content of cancer cell-derived exosomes. Front Oncol 2012; 2:38.
38. Meckes DG, Shair KH, Marquitz AR, Kung CP, Edwards RH, Raab-Traub N. Human tumor virus utilizes exosomes for intercellular communication. Proc Natl Acad Sci U S A 2010; 107:20370-20375.
39. Adamczyk KA, Klein-Scory S, Tehrani MM, Warnken U, Schmiegel W, Schnölzer M, et al. Characterization of soluble and exosomal forms of the EGFR released from pancreatic cancer cells. Life Sci 2011; 89:304-312.
40. Graner MW, Alzate O, Dechkovskaia AM, Keene JD, Sampson JH, Mitchell DA, et al. Proteomic and immunologic analyses of brain tumor exosomes. FASEB J 2009; 23:1541-1557.
41. Higginbotham JN, Demory Beckler M, Gephart JD, Franklin JL, Bogatcheva G, Kremers GJ, et al. Amphiregulin exosomes increase cancer cell invasion. Curr Biol 2011; 21:779-786.
42. 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; 9:2820-2835.
43. Mukhopadhyay UK, Mak AS. p53: is the guardian of the genome also a suppressor of cell invasion? Cell Cycle 2009; 8:2481.
44. Yu X, Harris SL, Levine AJ. The regulation of exosome secretion: a novel function of the p53 protein. Cancer Res 2006; 66:4795-4801.
45. Kharaziha P, Ceder S, Li Q, Panaretakis T. Tumor cell-derived exosomes: a message in a bottle. Biochim Biophys Acta 2012; 1826:103-111.
46. Hua KF, Hsu HY, Chao LK, Chen ST, Yang WB, Hsu J, et al. Ganoderma lucidum polysaccharides enhance CD14 endocytosis of LPS and promote TLR4 signal transduction of cytokine expression. J Cell Physiol 2007; 212:537-550.
47. Hao S, Ye Z, Li F, Meng Q, Qureshi M, Yang J, et al. Epigenetic transfer of metastatic activity by uptake of highly metastatic B16 melanoma cell-released exosomes. Exp Oncol 2006; 28:126-131.
48. Ristorcelli E, Beraud E, Mathieu S, Lombardo D, Verine A. Essential role of Notch signaling in apoptosis of human pancreatic tumoral cells mediated by exosomal nanoparticles. Int J Cancer 2009; 125:1016-1026.
49. Lim JW, Mathias RA, Kapp EA, Layton MJ, Faux MC, Burgess AW, et al. Restoration of full-length APC protein in SW480 colon cancer cells induces exosome-mediated secretion of DKK-4. Electrophoresis 2012; 33:1873-1880.
50. Naghibalhossaini F, Hosseini HM, Mokarram P, Zamani M. High frequency of genes' promoter methylation, but lack of BRAF V600E mutation among Iranian colorectal cancer patients. Pathol Oncol Res 2011; 17:819-825.
51. Putz U, Howitt J, Doan A, Goh CP, Low LH, Silke J, et al. The tumor suppressor PTEN is exported in exosomes and has phosphatase activity in recipient cells. Sci Signal 2012; 5:ra70.
52. Mineo M, Garfield SH, Taverna S, Flugy A, De Leo G, Alessandro R, et al. Exosomes released by K562 chronic myeloid leukemia cells promote angiogenesis in a Src-dependent fashion. Angiogenesis 2012; 15:33-45.
53. Muralidharan-Chari V, Clancy J, Plou C, Romao M, Chavrier P, Raposo G, et al. ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol 2009; 19:1875-1885.
54. Oeste CL, Pinar M, Schink KO, Martínez-Turrión J, Stenmark H, Peñalva MA, et al. An isoprenylation and palmitoylation motif promotes intraluminal vesicle delivery of proteins in cells from distant species. PLoS One 2014; 9:e107190.
55. Webber J, Steadman R, Mason MD, Tabi Z, Clayton A. Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer Res 2010; 70:9621-9630.
56. Cho JA, Park H, Lim EH, Lee KW. Exosomes from breast cancer cells can convert adipose tissue-derived mesenchymal stem cells into myofibroblast-like cells. Int J Oncol 2012; 40:130-138.
57. Jung T, Castellana D, Klingbeil P, Cuesta Hernández I, Vitacolonna M, Orlicky DJ, et al. CD44v6 dependence of premetastatic niche preparation by exosomes. Neoplasia 2009; 11:1093-10105.
58. Ristorcelli E, Beraud E, Verrando P, Villard C, Lafitte D, Sbarra V, et al. Human tumor nanoparticles induce apoptosis of pancreatic cancer cells. FASEB J 2008; 22:3358-3369.
59. Mahmoodzadeh Hosseini H, Imani Fooladi AA, Soleimanirad J, Nourani MR, Davaran S, Mahdavi M. Staphylococcal entorotoxin B anchored exosome induces apoptosis in negative esterogen receptor breast cancer cells. Tumour Biol 2014; 35:3699-3707.
60. Mahmoodzadeh Hosseini H, Imani Fooladi AA, Soleimanirad J, Nourani M, Mahdavi M. Exosome/staphylococcal enterotoxin B, an anti-tumor compound against pancreatic cancer. J BUON 2014; 19:440-448.
61. Mahmoodzadeh Hosseini H, Soleimanirad J, Mehdizadeh Aghdam E, Amin M, Imani Fooladi AA. Texosome-anchored superantigen triggers apoptosis in original ovarian cancer cells. Med Oncol 2015; 32:409.
62. Imani Fooladi AA, Halabian R, Mahdavi M, Amin M, Mahmoodzadeh Hosseini H. Staphylococcal enterotoxin B/texosomes as a candidate for breast cancer immunotherapy. Tumour Biol 2016; 37:739-748.
63. Abusamra AJ, Zhong Z, Zheng X, Li M, Ichim TE, Chin JL, et al. Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis. Blood Cells Mol Dis 2005; 35:169-173.
64. Mahmoodzadeh Hosseini H, Halabian R, Amin M, Imani Fooladi AA. Texosome-based drug delivery system for cancer therapy: from past to present. Cancer Biol Med 2015; 12:150-162.
65. Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 2008; 110:13-21.
66. Wu Q, Lu Z, Li H, Lu J, Guo L, Ge Q. Next-generation sequencing of microRNAs for breast cancer detection. Bio Med Res Int 2011; 2011.
67. Pigati L, Yaddanapudi SC, Iyengar R, Kim DJ, Hearn SA, Danforth D, et al. Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS One 2010; 5:e13515.
68. Rabinowits G, Gerçel-Taylor C, Day JM, Taylor DD, Kloecker GH. Exosomal microRNA: a diagnostic marker for lung cancer. Clin Lung Cancer 2009; 10:42-46.
69. Xiao D, Ohlendorf J, Chen Y, Taylor DD, Rai SN, Waigel S, et al. Identifying mRNA, microRNA and protein profiles of melanoma exosomes. PloS One 2012; 7:e46874.
70. Kanemaru H, Fukushima S, Yamashita J, Honda N, Oyama R, Kakimoto A, et al. The circulating microRNA-221 level in patients with malignant melanoma as a new tumor marker. J Dermatol Sci 2011; 61:187-193.
71. Bryant R, Pawlowski T, Catto J, Marsden G, Vessella R, Rhees B, et al. Changes in circulating microRNA levels associated with prostate cancer. Br J Cancer 2012; 106:768-774.
72. Liu R, Zhang C, Hu Z, Li G, Wang C, Yang C, et al. A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis. Eur J Cancer 2011; 47:784-791.
73. Kogure T, Lin WL, Yan IK, Braconi C, Patel T. Intercellular nanovesicle‐mediated microRNA transfer: A mechanism of environmental modulation of hepatocellular cancer cell growth. Hepatology 2011; 54:1237-1248.
74. Xu J, Wu C, Che X, Wang L, Yu D, Zhang T, et al. Circulating MicroRNAs, miR‐21, miR‐122, and miR‐223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog 2011; 50:136-142.
75. Montecalvo A, Larregina AT, Shufesky WJ, Stolz DB, Sullivan ML, Karlsson JM, et al. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 2012; 119:756-766.
76. Valadi H, , Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9:654-659.