细胞外囊泡在肝细胞癌及胆管癌诊治中的作用研究进展
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摘要
细胞外囊泡(extracellular vesicles,EVs)是细胞分泌的具有双层膜结构的微小囊泡,是细胞间物质交换和信息交流的重要媒介。近十年来EVs已逐渐发展成为肿瘤研究领域的一个热点话题,有研究发现EVs在肝细胞癌和胆管癌的发生发展中扮演十分关键的角色。EVs能够携带肝细胞癌和胆管癌细胞内特定的核酸、蛋白等特异性较强的分子物质,具有良好的疾病诊断价值;EVs可以通过调节免疫应答和运载核酸、蛋白质等至靶细胞、靶器官,起到调节肿瘤细胞生长、杀伤肿瘤细胞的作用,其独特的球形载体结构可为肝细胞癌和胆管癌的治疗提供全新的角度和方法。本文就EVs在肝细胞癌和胆管癌诊治中的作用研究进展作一综述。
引文
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[28]Wei JX,Lv LH,Wan YL,et al.Vps4A functions as a tumor suppressor by regulating the secretion and uptake of exosomal microRNAs in human hepatoma cells[J].Hepatology,2015,61(4):1284-1294.
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[31]Li L,Piontek K,Ishida M,et al.Extracellular vesicles carry microRNA-195 to intrahepatic cholangiocarcinoma and improve survival in a rat model[J].Hepatology,2017,65(2):501-514.
[2]Huang A,Dong J,Li S,et al.Exosomal transfer of vasorin expressed in hepatocellular carcinoma cells promotes migration of human umbilical vein endothelial cells[J].Int J Biol Sci,2015,11(8):961-969.
[3]He M,Qin H,Poon TC,et al,Hepatocellular carcinoma-derived exosomes promote motility of immortalized hepatocyte through transfer of oncogenic proteins and RNAs[J].Carcinogenesis,2015,36(9):1008-1018.
[4]Borrelli DA,Yankson K,Shukla N,et al.Extracellular vesicle therapeutics for liver disease[J].J Control Release,2018,273:86-98.
[5]何其宽,戴宁高,叶瑞凡,等.干细胞来源外泌体对大鼠肝脏缺血再灌注损伤的保护作用[J].肝胆胰外科杂志,2018,30(2):134-141.
[6]Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
[7]Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[8]Patel T.Cholangiocarcinoma-controversies and challenges[J].Nat Rev Gastroenterol Hepatol,2011,8(4):189-200.
[9]Crispe IN.The liver as a lymphoid organ[J].Annu Rev Immunol,2009,27:147-163.
[10]Masyuk AI,Masyuk TV,Larusso NF.Exosomes in the pathogenesis,diagnostics and therapeutics of liver diseases[J].JHepatol,2013,59(3):621-625.
[11]Momen-Heravi,Bala S,Kodys K,et al.Exosomes derived from alcohol-treated hepatocytes horizontally transfer liver specific miRNA-122 and sensitize monocytes to LPS[J].Sci Rep,2015,5:9991.
[12]Li L,Piontek KB,Kumbhari V,et al.Isolation and profiling of MicroRNA-containing exosomes from human bile[J].J Vis Exp,2016,112:e54036.
[13]Masyuk AI,Huang BQ,Ward CJ,et al.Biliary exosomes influence cholangiocyte regulatory mechanisms and proliferation through interaction with primary cilia[J].Am J Physiol Gastrointest Liver Physiol,2010,299(4):G990-999.
[14]Wang Y,Wang G,Wang Z,et al.Chicken biliary exosomes enhance CD4(+)T proliferation and inhibit ALV-J replication in liver[J].Biochem Cell Biol,2014,92(2):145-151.
[15]Severino V,Dumonceau JM,Delhaye M,et al.Extracellular vesicles in bile as markers of malignant biliary stenoses[J].Gastroenterology,2017,153(2):495-504.
[16]Chen L,Chen R,Kemper S,et al.Suppression of fibrogenic signaling in hepatic stellate cells by Twist1-dependent microRNA-214 expression:Role of exosomes in horizontal transfer of Twist1[J].Am J Physiol Gastrointest Liver Physiol,2015,309(6):G491-499.
[17]Charrier A,Chen R,Chen L,et al.Exosomes mediate intercellular transfer of pro-fibrogenic connective tissue growth factor(CCN2)between hepatic stellate cells,the principal fibrotic cells in the liver[J].Surgery,2014,156(3):548-555.
[18]Taylor DD,Gercel-Taylor C.MicroRNA signatures of tumorderived exosomes as diagnostic biomarkers of ovarian cancer[J].Gynecol Oncol,2008,110(1):13-21.
[19]Rabinowits G,Gercel-Taylor C,Day JM,et al.Exosomal microRNA:a diagnostic marker for lung cancer[J].Clin Lung Cancer,2009,10(1):42-46.
[20]Melo SA,Luecke LB,Kahlert C,et al.Glypican-1 identifies cancer exosomes and detects early pancreatic cancer[J].Nature,2015,523(7559):177-182.
[21]Valadi H,Ekstrom K,Bossios A,et al.Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells[J].Nat Cell Biol,2007,9(6):654-659.
[22]Bobrie A,Krumeich S,Reyal F,et al.Rab27a supports exosome-dependent and-independent mechanisms that modify the tumor microenvironment and can promote tumor progression[J].Cancer Res,2012,72(19):4920-4930.
[23]Sohn W,Kim J,Kang SH,et al.Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma[J].Exp Mol Med,2015,47:e184.
[24]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[J].Br J Cancer,2015,112(3):532-538.
[25]Wang H,Hou L,Li A,et al.Expression of serum exosomal micro RNA-21 in human hepatocellular carcinoma[J].Biomed Res Int,2014,2014:864894.
[26]Arbelaiz A,Azkargorta M,Krawczyk M,et al.Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma[J].Hepatology,2017,66(4):1125-1143.
[27]Li L,Masica D,Ishida M,et al.Human bile contains microR-NA-laden extracellular vesicles that can be used for cholangiocarcinoma diagnosis[J].Hepatology,2014,60(3):896-907.
[28]Wei JX,Lv LH,Wan YL,et al.Vps4A functions as a tumor suppressor by regulating the secretion and uptake of exosomal microRNAs in human hepatoma cells[J].Hepatology,2015,61(4):1284-1294.
[29]Lou G,Song X,Yang F,et al.Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma[J].J Hematol Oncol,2015,8:122.
[30]Tang K,Zhang Y,Zhang H,et al.Delivery of chemotherapeutic drugs in tumour cell-derived microparticles[J].Nat Commun,2012,3:1282.
[31]Li L,Piontek K,Ishida M,et al.Extracellular vesicles carry microRNA-195 to intrahepatic cholangiocarcinoma and improve survival in a rat model[J].Hepatology,2017,65(2):501-514.
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