Role of exosomes and exosomal microRNAs in hepatocellular carcinoma: Potential in diagnosis and antitumour treatments (Review)
- Authors:
- Jing‑Hua Pan
- Hong Zhou
- Xiao‑Xu Zhao
- Hui Ding
- Wei Li
- Li Qin
- Yun‑Long Pan
-
Affiliations: Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, P.R. China, Department of Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, P.R. China, Department of Histology and Embryology, Medical School of Jinan University, Guangzhou, Guangdong 510632, P.R. China - Published online on: January 11, 2018 https://doi.org/10.3892/ijmm.2018.3383
- Pages: 1809-1816
-
Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI | |
El-Serag HB and Rudolph KL: Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology. 132:2557–2576. 2007. View Article : Google Scholar : PubMed/NCBI | |
El-Serag HB: Hepatocellular carcinoma. N Engl J Med. 365:1118–1127. 2011. View Article : Google Scholar : PubMed/NCBI | |
Jeon Y, Jang ES, Choi YS, Kim JW and Jeong SH: Glypican-3 level assessed by the enzyme-linked immunosorbent assay is inferior to alpha-fetoprotein level for hepatocellular carcinoma diagnosis. Clin Mol Hepatol. 22:359–365. 2016. View Article : Google Scholar : PubMed/NCBI | |
Milane L, Singh A, Mattheolabakis G, Suresh M and Amiji MM: Exosome mediated communication within the tumor microenvironment. J Control Release. 219:278–294. 2015. View Article : Google Scholar : PubMed/NCBI | |
Yu DD, Wu Y, Shen HY, Lv MM, Chen WX, Zhang XH, Zhong SL, Tang JH and Zhao JH: Exosomes in development, metastasis and drug resistance of breast cancer. Cancer Sci. 106:959–964. 2015. View Article : Google Scholar : PubMed/NCBI | |
Tang Y, Cui Y, Li Z, Jiao Z, Zhang Y, He Y, Chen G, Zhou Q, Wang W, Zhou X, et al: Radiation-induced miR-208a increases the proliferation and radioresistance by targeting p21 in human lung cancer cells. J Exp Clin Cancer Res. 35:72016. View Article : Google Scholar : PubMed/NCBI | |
Soung YH, Nguyen T, Cao H, Lee J and Chung J: Emerging roles of exosomes in cancer invasion and metastasis. BMB Rep. 49:18–25. 2016. View Article : Google Scholar : | |
Riches A, Campbell E, Borger E and Powis S: Regulation of exosome release from mammary epithelial and breast cancer cells - a new regulatory pathway. Eur J Cancer. 50:1025–1034. 2014. View Article : Google Scholar : PubMed/NCBI | |
Yang N, Li S, Li G, Zhang S, Tang X, Ni S, Jian X, Xu C, Zhu J and Lu M: The role of extracellular vesicles in mediating progression, metastasis and potential treatment of hepatocellular carcinoma. Oncotarget. 8:3683–3695. 2017. | |
Wang Z, Chen JQ, Liu JL and Tian L: Exosomes in tumor microenvironment: Novel transporters and biomarkers. J Transl Med. 14:2972016. View Article : Google Scholar : PubMed/NCBI | |
Théry C, Zitvogel L and Amigorena S: Exosomes: Composition, biogenesis and function. Nat Rev Immunol. 2:569–579. 2002. View Article : Google Scholar : PubMed/NCBI | |
Wolf P: The nature and significance of platelet products in human plasma. Br J Haematol. 13:269–288. 1967. View Article : Google Scholar : PubMed/NCBI | |
Harding C, Heuser J and Stahl P: Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol. 97:329–339. 1983. View Article : Google Scholar : PubMed/NCBI | |
Johnstone RM, Adam M, Hammond JR, Orr L and Turbide C: Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem. 262:9412–9420. 1987.PubMed/NCBI | |
Mathivanan S, Ji H and Simpson RJ: Exosomes: Extracellular organelles important in intercellular communication. J Proteomics. 73:1907–1920. 2010. View Article : Google Scholar : PubMed/NCBI | |
Oosthuyzen W, Sime NE, Ivy JR, Turtle EJ, Street JM, Pound J, Bath LE, Webb DJ, Gregory CD, Bailey MA, et al: Quantification of human urinary exosomes by nanoparticle tracking analysis. J Physiol. 591:5833–5842. 2013. View Article : Google Scholar : PubMed/NCBI | |
Street JM, Barran PE, Mackay CL, Weidt S, Balmforth C, Walsh TS, Chalmers RT, Webb DJ and Dear JW: Identification and proteomic profiling of exosomes in human cerebrospinal fluid. J Transl Med. 10:52012. View Article : Google Scholar : PubMed/NCBI | |
Wang H, Hou L, Li A, Duan Y, Gao H and Song X: Expression of serum exosomal microRNA-21 in human hepatocellular carcinoma. Biomed Res Int. 2014:8648942014.PubMed/NCBI | |
Kogure T, Lin WL, Yan IK, Braconi C and Patel T: Intercellular nanovesicle-mediated microRNA transfer: A mechanism of environmental modulation of hepatocellular cancer cell growth. Hepatology. 54:1237–1248. 2011. View Article : Google Scholar : PubMed/NCBI | |
Yuyama K, Sun H, Mitsutake S and Igarashi Y: Sphingolipid-modulated exosome secretion promotes clearance of amyloid-β by microglia. J Biol Chem. 287:10977–10989. 2012. View Article : Google Scholar : PubMed/NCBI | |
Herreros-Villanueva M and Bujanda L: Glypican-1 in exosomes as biomarker for early detection of pancreatic cancer. Ann Transl Med. 4:642016.PubMed/NCBI | |
Ludwig AK and Giebel B: Exosomes: Small vesicles participating in intercellular communication. Int J Biochem Cell Biol. 44:11–15. 2012. View Article : Google Scholar | |
Tkach M and Théry C: Communication by extracellular vesicles: Where we are and where we need to go. Cell. 164:1226–1232. 2016. View Article : Google Scholar : PubMed/NCBI | |
Shrivastava S, Devhare P, Sujijantarat N, Steele R, Kwon YC, Ray R and Ray RB: Knockdown of autophagy inhibits infectious hepatitis C virus release by the exosomal pathway. J Virol. 90:1387–1396. 2015. View Article : Google Scholar : PubMed/NCBI | |
Conigliaro A, Costa V, Lo Dico A, Saieva L, Buccheri S, Dieli F, Manno M, Raccosta S, Mancone C, Tripodi M, et al: CD90+ liver cancer cells modulate endothelial cell phenotype through the release of exosomes containing H19 lncRNA. Mol Cancer. 14:1552015. View Article : Google Scholar | |
Aucher A, Rudnicka D and Davis DM: MicroRNAs transfer from human macrophages to hepato-carcinoma cells and inhibit proliferation. J Immunol. 191:6250–6260. 2013. View Article : Google Scholar : PubMed/NCBI | |
Putz U, Howitt J, Doan A, Goh CP, Low LH, Silke J and Tan SS: The tumor suppressor PTEN is exported in exosomes and has phosphatase activity in recipient cells. Sci Signal. 5:ra702012. View Article : Google Scholar : PubMed/NCBI | |
Azmi AS, Bao B and Sarkar FH: Exosomes in cancer development, metastasis, and drug resistance: A comprehensive review. Cancer Metastasis Rev. 32:623–642. 2013. View Article : Google Scholar : PubMed/NCBI | |
Whiteside TL: Immune modulation of T-cell and NK (natural killer) cell activities by TEXs (tumour-derived exosomes). Biochem Soc Trans. 41:245–251. 2013. View Article : Google Scholar : PubMed/NCBI | |
Chiba M, Kimura M and 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. 28:1551–1558. 2012. View Article : Google Scholar : PubMed/NCBI | |
Xu Y, Xia F, Ma L, Shan J, Shen J, Yang Z, Liu J, Cui Y, Bian X, Bie P, et al: MicroRNA-122 sensitizes HCC cancer cells to adriamycin and vincristine through modulating expression of MDR and inducing cell cycle arrest. Cancer Lett. 310:160–169. 2011.PubMed/NCBI | |
Wang B, Majumder S, Nuovo G, Kutay H, Volinia S, Patel T, Schmittgen TD, Croce C, Ghoshal K and Jacob ST: Role of microRNA-155 at early stages of hepatocarcinogenesis induced by choline-deficient and amino acid-defined diet in C57BL/6 mice. Hepatology. 50:1152–1161. 2009. View Article : Google Scholar : PubMed/NCBI | |
Li S, Fu H, Wang Y, Tie Y, Xing R, Zhu J, Sun Z, Wei L and Zheng X: MicroRNA-101 regulates expression of the v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) oncogene in human hepatocellular carcinoma. Hepatology. 49:1194–1202. 2009. View Article : Google Scholar : PubMed/NCBI | |
Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST and Patel T: MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 133:647–658. 2007. View Article : Google Scholar : PubMed/NCBI | |
Varnholt H, Drebber U, Schulze F, Wedemeyer I, Schirmacher P, Dienes HP and Odenthal M: MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma. Hepatology. 47:1223–1232. 2008. View Article : Google Scholar : PubMed/NCBI | |
Yang YF, Wang F, Xiao JJ, Song Y, Zhao YY, Cao Y, Bei YH and Yang CQ: MiR-222 overexpression promotes proliferation of human hepatocellular carcinoma HepG2 cells by downregulating p27. Int J Clin Exp Med. 7:893–902. 2014.PubMed/NCBI | |
Gramantieri L, Ferracin M, Fornari F, Veronese A, Sabbioni S, Liu CG, Calin GA, Giovannini C, Ferrazzi E, Grazi GL, et al: Cyclin G1 is a target of miR-122a, a microRNA frequently downregulated in human hepatocellular carcinoma. Cancer Res. 67:6092–6099. 2007. View Article : Google Scholar : PubMed/NCBI | |
Wang G, Zhu S, Gu Y, Chen Q, Liu X and Fu H: MicroRNA-145 and microRNA-133a inhibited proliferation, migration, and invasion, while promoted apoptosis in hepatocellular carcinoma cells via targeting FSCN1. Dig Dis Sci. 60:3044–3052. 2015. View Article : Google Scholar : PubMed/NCBI | |
Wang Q, Yu X, Li Q, Qin L, Tan S, Zeng X, Qiu X, Tang B, Jin J, Liao W, et al: Association between miR-199a rs74723057 and MET rs1621 polymorphisms and the risk of hepatocellular carcinoma. Oncotarget. 7:79365–79371. 2016.PubMed/NCBI | |
Huang XH, Wang Q, Chen JS, Fu XH, Chen XL, Chen LZ, Li W, Bi J, Zhang LJ, Fu Q, et al: Bead-based microarray analysis of microRNA expression in hepatocellular carcinoma: miR-338 is downregulated. Hepatol Res. 39:786–794. 2009. View Article : Google Scholar : PubMed/NCBI | |
Fornari F, Ferracin M, Trerè D, Milazzo M, Marinelli S, Galassi M, Venerandi L, Pollutri D, Patrizi C, Borghi A, et al: Circulating microRNAs, miR-939, miR-595, miR-519d and miR-494, identify cirrhotic patients with HCC. PLoS One. 10:e01414482015. View Article : Google Scholar : PubMed/NCBI | |
Li Y, Zhang L, Liu F, Xiang G, Jiang D and Pu X: Identification of endogenous controls for analyzing serum exosomal miRNA in patients with hepatitis B or hepatocellular carcinoma. Dis Markers. 2015:8935942015. View Article : Google Scholar : PubMed/NCBI | |
Wei JX, Lv LH, Wan YL, Cao Y, Li GL, Lin HM, Zhou R, Shang CZ, Cao J, He H, et al: Vps4A functions as a tumor suppressor by regulating the secretion and uptake of exosomal microRNAs in human hepatoma cells. Hepatology. 61:1284–1294. 2015. View Article : Google Scholar : | |
Basu S and Bhattacharyya SN: Insulin-like growth factor-1 prevents miR-122 production in neighbouring cells to curtail its intercellular transfer to ensure proliferation of human hepatoma cells. Nucleic Acids Res. 42:7170–7185. 2014. View Article : Google Scholar : PubMed/NCBI | |
Lou G, Song X, Yang F, Wu S, Wang J, Chen Z and Liu Y: Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. J Hematol Oncol. 8:1222015. View Article : Google Scholar : PubMed/NCBI | |
Pan Q, Ramakrishnaiah V, Henry S, Fouraschen S, de Ruiter PE, Kwekkeboom J, Tilanus HW, Janssen HL and van der Laan LJ: Hepatic cell-to-cell transmission of small silencing RNA can extend the therapeutic reach of RNA interference (RNAi). Gut. 61:1330–1339. 2012. View Article : Google Scholar | |
Sugimachi K, Matsumura T, Hirata H, Uchi R, Ueda M, Ueo H, Shinden Y, Iguchi T, Eguchi H, Shirabe K, et al: Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation. Br J Cancer. 112:532–538. 2015. View Article : Google Scholar : PubMed/NCBI | |
Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, de Gruijl TD, Würdinger T and Middeldorp JM: Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci USA. 107:6328–6333. 2010. View Article : Google Scholar : PubMed/NCBI | |
Xiao W, Dong W, Zhang C, Saren G, Geng P, Zhao H, Li Q, Zhu J, Li G, Zhang S, et al: Effects of the epigenetic drug MS-275 on the release and function of exosome-related immune molecules in hepatocellular carcinoma cells. Eur J Med Res. 18:612013. View Article : Google Scholar : PubMed/NCBI | |
Feng Z, Hensley L, McKnight KL, Hu F, Madden V, Ping L, Jeong SH, Walker C, Lanford RE and Lemon SM: A pathogenic picornavirus acquires an envelope by hijacking cellular membranes. Nature. 496:367–371. 2013. View Article : Google Scholar : PubMed/NCBI | |
Ramakrishnaiah V, Thumann C, Fofana I, Habersetzer F, Pan Q, de Ruiter PE, Willemsen R, Demmers JA, Stalin Raj V, Jenster G, et al: Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells. Proc Natl Acad Sci USA. 110:13109–13113. 2013. View Article : Google Scholar : PubMed/NCBI | |
Chen TC, Hsieh CH and Sarnow P: Supporting role for GTPase Rab27a in hepatitis C virus RNA replication through a novel miR-122-mediated effect. PLoS Pathog. 11:e10051162015. View Article : Google Scholar : PubMed/NCBI | |
Tickner JA, Urquhart AJ, Stephenson SA, Richard DJ and O'Byrne KJ: Functions and therapeutic roles of exosomes in cancer. Front Oncol. 4:1272014. View Article : Google Scholar : PubMed/NCBI | |
Huang A, Dong J, Li S, Wang C, Ding H, Li H, Su X, Ge X, Sun L, Bai C, et al: Exosomal transfer of vasorin expressed in hepatocellular carcinoma cells promotes migration of human umbilical vein endothelial cells. Int J Biol Sci. 11:961–969. 2015. View Article : Google Scholar : PubMed/NCBI | |
He M, Qin H, Poon TC, Sze SC, Ding X, Co NN, Ngai SM, Chan TF and Wong N: Hepatocellular carcinoma-derived exosomes promote motility of immortalized hepatocyte through transfer of oncogenic proteins and RNAs. Carcinogenesis. 36:1008–1018. 2015. View Article : Google Scholar : PubMed/NCBI | |
Chiba M, Watanabe N, Watanabe M, Sakamoto M, Sato A, Fujisaki M, Kubota S, Monzen S, Maruyama A, Nanashima N, et al: Exosomes derived from SW480 colorectal cancer cells promote cell migration in HepG2 hepatocellular cancer cells via the mitogen-activated protein kinase pathway. Int J Oncol. 48:305–312. 2016. View Article : Google Scholar | |
Liu WH, Ren LN, Wang X, Wang T, Zhang N, Gao Y, Luo H, Navarro-Alvarez N and Tang LJ: Combination of exosomes and circulating microRNAs may serve as a promising tumor marker complementary to alpha-fetoprotein for early-stage hepatocellular carcinoma diagnosis in rats. J Cancer Res Clin Oncol. 141:1767–1778. 2015. View Article : Google Scholar : PubMed/NCBI | |
Li Y, Xiang GM, Liu LL, Liu C, Liu F, Jiang DN and Pu XY: Assessment of endogenous reference gene suitability for serum exosomal microRNA expression analysis in liver carcinoma resection studies. Mol Med Rep. 12:4683–4691. 2015. View Article : Google Scholar : PubMed/NCBI | |
Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, LeBleu VS, Mittendorf EA, Weitz J, Rahbari N, et al: Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature. 523:177–182. 2015. View Article : Google Scholar : PubMed/NCBI | |
Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT Jr, Carter BS, Krichevsky AM and Breakefield XO: Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 10:1470–1476. 2008. View Article : Google Scholar : PubMed/NCBI | |
Tanaka Y, Kamohara H, Kinoshita K, Kurashige J, Ishimoto T, Iwatsuki M, Watanabe M and Baba H: Clinical impact of serum exosomal microRNA-21 as a clinical biomarker in human esophageal squamous cell carcinoma. Cancer. 119:1159–1167. 2013. View Article : Google Scholar | |
Sohn W, Kim J, Kang SH, Yang SR, Cho JY, Cho HC, Shim SG and Paik YH: Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma. Exp Mol Med. 47:e1842015. View Article : Google Scholar : PubMed/NCBI | |
Kogure T, Yan IK, Lin WL and Patel T: Extracellular vesicle-mediated transfer of a novel long noncoding RNA TUC339: A mechanism of intercellular signaling in human hepatocellular cancer. Genes Cancer. 4:261–272. 2013. View Article : Google Scholar : PubMed/NCBI | |
Mohankumar S and Patel T: Extracellular vesicle long noncoding RNA as potential biomarkers of liver cancer. Brief Funct Genomics. 15:249–256. 2016. View Article : Google Scholar : | |
Bandiera S, Pfeffer S, Baumert TF and Zeisel MB: miR-122 - a key factor and therapeutic target in liver disease. J Hepatol. 62:448–457. 2015. View Article : Google Scholar | |
Mou DL, Jia ZS and Bai XF: Exosome: Trojan horse in immunotherapy. Sheng Li Ke Xue Jin Zhan. 36:113–118. 2005.In Chinese. PubMed/NCBI | |
Wang SH, Shen Y, Li J, Xiang ZW, Fan WK and Chen L: Experimental studies on anti-mouse hepatocellular carcinoma effects of cisplatin combined with exosomes. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 25:49–52. 2009.In Chinese. PubMed/NCBI | |
Qu Z, Wu J, Wu J, Luo D, Jiang C and Ding Y: Exosomes derived from HCC cells induce sorafenib resistance in hepatocellular carcinoma both in vivo and in vitro. J Exp Clin Cancer Res. 35:1592016. View Article : Google Scholar : PubMed/NCBI | |
Ma B, Jiang H, Jia J, Di L, Song G, Yu J, Zhu Y, Lu Z, Wang X, Zhou X, et al: Murine bone marrow stromal cells pulsed with homologous tumor-derived exosomes inhibit proliferation of liver cancer cells. Clin Transl Oncol. 14:764–773. 2012. View Article : Google Scholar : PubMed/NCBI | |
Xiao WH, Sanren GW, Zhu JH, Li QW, Kang HR, Wang RL, Song LP and Ye M: Effect of 5-aza-2′-deoxycytidine on immune-associated proteins in exosomes from hepatoma. World J Gastroenterol. 16:2371–2377. 2010. View Article : Google Scholar : PubMed/NCBI | |
Li QW, Xiao WH, Sarengaowa G, Dong WW, Zhao HX, Duan XY, Zhu JH, Kang HR, Fu Y, Hao YX, et al: Histone deacetylase inhibitor MS-275 treatment alters immune molecule content and categories in hepatocarcinoma exosomes. Zhonghua Gan Zang Bing Za Zhi. 20:231–235. 2012.In Chinese. PubMed/NCBI | |
Ko SF, Yip HK, Zhen YY, Lee CC, Lee CC, Huang CC, Ng SH and Lin JW: Adipose-derived mesenchymal stem cell exosomes suppress hepatocellular carcinoma growth in a rat model: Apparent diffusion coefficient, natural killer T-cell responses, and histopathological features. Stem Cells Int. 2015:8535062015. View Article : Google Scholar : PubMed/NCBI | |
Zhou W, Fong MY, Min Y, Somlo G, Liu L, Palomares MR, Yu Y, Chow A, O'Connor ST, Chin AR, et al: Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell. 25:501–515. 2014. View Article : Google Scholar : PubMed/NCBI | |
Mincheva-Nilsson L, Baranov V, Nagaeva O and Dehlin E: Isolation and characterization of exosomes from cultures of tissue explants and cell lines. Curr Protoc Immunol. 115:14.42.1–14.42.21. 2016. View Article : Google Scholar | |
Lötvall J, Hill AF, Hochberg F, Buzás EI, Di Vizio D, Gardiner C, Gho YS, Kurochkin IV, Mathivanan S, Quesenberry P, et al: Minimal experimental requirements for definition of extracellular vesicles and their functions: A position statement from the International Society for Extracellular Vesicles. J Extracell Vesicles. 3:269132014. View Article : Google Scholar : PubMed/NCBI | |
Bobrie A and Théry C: Exosomes and communication between tumours and the immune system: Are all exosomes equal. Biochem Soc Trans. 41:263–267. 2013. View Article : Google Scholar : PubMed/NCBI | |
Viaud S, Ploix S, Lapierre V, Théry C, Commere PH, Tramalloni D, Gorrichon K, Virault-Rocroy P, Tursz T, Lantz O, et al: Updated technology to produce highly immunogenic dendritic cell-derived exosomes of clinical grade: a critical role of interferon-gamma. J Immunother. 34:65–75. 2011. View Article : Google Scholar | |
Dai S, Wei D, Wu Z, Zhou X, Wei X, Huang H and Li G: Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer. Mol Ther. 16:782–790. 2008. View Article : Google Scholar : PubMed/NCBI |