外泌体在肿瘤形成及诊疗中的作用

doi:10.3760/cma.j.issn.1673-422X.2018.12.008

摘要/Abstract

摘要： 外泌体是正常细胞与肿瘤细胞均会分泌的膜性亚细胞结构，内含多种特定微小RNA（miRNA）及信号分子，在肿瘤的形成机制、诊断分型以及免疫治疗中均具有重要研究价值。外泌体对肿瘤发生发展具有双刃剑作用，其内含的miRNA作为分子标记有助于对胶质母细胞瘤等形态学上疑难的肿瘤进行分型，而在肿瘤治疗中，外泌体既可以作为药物载体，又可以通过自身特性实现新型免疫治疗。

关键词: 肿瘤, 诊断, 免疫疗法, 外泌体

Abstract: Exosomes are subcellular membrane structures secreted by both normal cells and tumor cells. They contain a variety of specific microRNAs (miRNAs) and signaling molecules, and have important research value in tumorigenesis, tumor diagnostic classification and immunotherapy. The effect of exosomes on tumorigenesis is a doubleedged sword, and the miRNAs act as molecular markers and contribute to classify morphologically intractable tumors such as glioblastoma. In antineoplastic therapy, exosomes can be used as drug carriers or induce a new type of immunotherapy through their own characteristics.

Key words: Neoplasms, Diagnosis, Immunotherapy, Exosomes

杨鑫，孟斌. 外泌体在肿瘤形成及诊疗中的作用[J]. 国际肿瘤学杂志, 2018, 45(12): 739-742.

Yang Xin, Meng Bin. Roles of exosomes in tumor formation, diagnosis and treatment[J]. Journal of International Oncology, 2018, 45(12): 739-742.

参考文献

［1］ Zitvogel L, Regnault A, Lozier A, et al. Eradication of established murine tumors using a novel cellfree vaccine: dendritic cellderived exosomes［J］. Nat Med, 1998, 4(5): 594600. DOI: 10.1038/nm0598594. ［2］ Kojima M, Costantini TW, Eliceiri BP, et al. Gut epithelial cellderived exosomes trigger posttrauma immune dysfunction［J］. J Trauma Acute Care Surg, 2018, 84(2): 257264. DOI: 10.1097/TA.0000000000001748. ［3］ Brisson AR, Tan S, Linares R, et al. Extracellular vesicles from activated platelets: a semiquantitative cryoelectron microscopy and immunogold labeling study［J］. Platelets, 2017, 28(3): 263271. DOI: 10.1080/09537104.2016.1268255. ［4］ Saadatpour L, Fadaee E, Fadaei S, et al. Glioblastoma: exosome and microRNA as novel diagnosis biomarkers［J］. Cancer Gene Ther, 2016, 23(12): 415418. DOI: 10.1038/cgt.2016.48. ［5］ Kosaka N, Izumi H, Sekine K, et al. MicroRNA as a new immuneregulatory agent in breast milk［J］. Silence, 2010, 1(1): 7. DOI: 10.1186/1758907X17. ［6］ Milane L, Singh A, Mattheolabakis G, et al. Exosome mediated communication within the tumor microenvironment［J］. J Control Release, 2015, 219: 278294. DOI: 10.1016/j.jconrel.2015.06.029. ［7］ Zhitomirsky B, Assaraf YG. Lysosomes as mediators of drug resistance in cancer［J］. Drug Resist Updat, 2016, 24: 2333. DOI: 10.1016/j.drup.2015.11.004. ［8］ Wang J, Li D, Zhuang Y, et al. Exosomes derived from bone marrow stromal cells decrease the sensitivity of leukemic cells to etoposide［J］. Oncol Lett, 2017, 14(3): 30823088. DOI: 10.3892/ol.2017.6509. ［9］崔焱, 于津浦, 李慧, 等. 肿瘤细胞来源胞外体的分离鉴定与功能检测［J］. 天津医药, 2009, 37(12): 10141016. DOI: 10.3969/j.issn.02539896.2009.12.007. ［10］李慧, 岳欣, 张澎, 等. 肿瘤细胞来源的胞外体对CIK细胞活性的影响［J］. 中华微生物学和免疫学杂志, 2007, 27(6): 504508. DOI: 10.3760/j:issn:02545101.2007.06.005. ［11］ Syn N, Wang L, Sethi G, et al. Exosomemediated metastasis: from epithelialmesenchymal transition to escape from immunosurveillance［J］. Trends Pharmacol Sci, 2016, 37(7): 606617. DOI: 10.1016/j.tips.2016.04.006. ［12］ Giusti I, Delle Monache S, Di Francesco M, et al. From glioblastoma to endothelial cells through extracellular vesicles: messages for angiogenesis［J］. Tumour Biol, 2016, 37(9): 1274312753. DOI: 10.1007/s1327701651650. ［13］ Tadokoro H, Umezu T, Ohyashiki K, et al. Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells［J］. J Biol Chem, 2013, 288(48): 3434334351. DOI: 10.1074/jbc.M113.480822. ［14］ King HW, Michael MZ, Gleadle JM. Hypoxic enhancement of exosome release by breast cancer cells［J］. BMC Cancer, 2012, 12: 421. DOI: 10.1186/1471240712421. ［15］ Hedlund M, Nagaeva O, Kargl D, et al. Thermal and oxidative stress causes enhanced release of NKG2D ligandbearing immunosuppressive exosomes in leukemia/lymphoma T and B cells［J］. PLoS One, 2011, 6(2): e16899. DOI: 10.1371/journal.pone.0016899. ［16］ Reiners KS, Topolar D, Henke A, et al. Soluble ligands for NK cell receptors promote evasion of chronic lymphocytic leukemia cells from NK cell antitumor activity［J］. Blood, 2013, 121(18): 36583665. DOI: 10.1182/blood201301476606. ［17］ Chen W, Wang J, Shao C, et al. Efficient induction of antitumor T cell immunity by exosomes derived from heatshocked lymphoma cells［J］. Eur J Immunol, 2006, 36(6): 15981607. DOI: 10.1002/eji.200535501. ［18］ Teow SY, Yap HY, Peh SC. EpsteinBarr virus as a promising immunotherapeutic target for nasopharyngeal carcinoma treatment［J］. J Pathog, 2017, 2017: 7349268. DOI: 10.1155/2017/7349268. ［19］ Piccaluga PP, Weber A, Ambrosio MR, et al. EpsteinBarr virusinduced metabolic rearrangements in human Bcell lymphomas［J］. Front Microbiol, 2018, 9: 1233. DOI: 10.3389/fmicb.2018.01233. ［20］ Meckes DG Jr, RaabTraub N. Microvesicles and viral infection［J］. J Virol, 2011, 85(24): 1284412854. DOI: 10.1128/JVI.0585311. ［21］ Dolcetti R. Crosstalk between EpsteinBarr virus and microenvironment in the pathogenesis of lymphomas［J］. Semin Cancer Biol, 2015, 34: 5869. DOI: 10.1016/j.semcancer.2015.04.006. ［22］ Barth S, Meister G, Grsser FA. EBVencoded miRNAs［J］. Biochim Biophys Acta, 2011, 1809(1112): 631640. DOI: 10.1016/j.bbagrm.2011.05.010. ［23］ Harold C, Cox D, Riley KJ. EpsteinBarr viral microRNAs target caspase 3［J］. Virol J, 2016, 13: 145. DOI: 10.1186/s1298501606027. ［24］ Gallo A, Vella S, Miele M, et al. Global profiling of viral and cellular noncoding RNAs in EpsteinBarr virusinduced lymphoblastoid cell lines and released exosome cargos［J］. Cancer Lett, 2017, 388: 334343. DOI: 10.1016/j.canlet.2016.12.003. ［25］ Li Z, Chen X, Li L, et al. EBV encoded miRBHRF11 potentiates viral lytic replication by downregulating host p53 in nasopharyngeal carcinoma［J］. Int J Biochem Cell Biol, 2012, 44(2): 275279. DOI: 10.1016/j.biocel.2011.11.007. ［26］ Ahmed W, Philip PS, Attoub S, et al. EpsteinBarr virusinfected cells release Fas ligand in exosomal fractions and induce apoptosis in recipient cells via the extrinsic pathway［J］. J Gen Virol, 2015, 96(12): 36463659. DOI: 10.1099/jgv.0.000313. ［27］ Rialland P, Lankar D, Raposo G, et al. BCRbound antigen is targeted to exosomes in human follicular lymphoma Bcells［J］. Biol Cell, 2006, 98(8): 491501. DOI: 10.1042/BC20060027. ［28］ HazanHalevy I, Rosenblum D, Weinstein S, et al. Cellspecific uptake of mantle cell lymphomaderived exosomes by malignant and nonmalignant Blymphocytes［J］. Cancer Lett, 2015, 364(1): 5969. DOI: 10.1016/j.canlet.2015.04.026. ［29］ Nanbo A, Kawanishi E, Yoshida R, et al. Exosomes derived from EpsteinBarr virusinfected cells are internalized via caveoladependent endocytosis and promote phenotypic modulation in target cells［J］. J Virol, 2013, 87(18): 1033410347. DOI: 10.1128/JVI.0131013. ［30］ Svensson KJ, Christianson HC, Wittrup A, et al. Exosome uptake depends on ERK1/2heat shock protein 27 signaling and lipid Raftmediated endocytosis negatively regulated by caveolin1［J］. J Biol Chem, 2013, 288(24): 1771317724. DOI: 10.1074/jbc.M112.445403. ［31］ Bouvy C, Wannez A, George F, et al. Circulating microRNAs as biomarkers in diffuse large Bcell lymphoma: a pilot prospective longitudinal clinical study［J］. Biomark Cancer, 2018, 10: 1179299X18781095. DOI: 10.1177/1179299X18781095. ［32］ Tomasetti M, Lee W, Santarelli L, et al. Exosomederived microRNAs in cancer metabolism: possible implications in cancer diagnostics and therapy［J］. Exp Mol Med, 2017, 49(1): e285. DOI: 10.1038/emm.2016.153. ［33］ Ren J, He W, Zheng L, et al. From structures to functions: insights into exosomes as promising drug delivery vehicles［J］. Biomater Sci, 2016, 4(6): 910921. DOI: 10.1039/c5bm00583c.

[1]	刘娜, 寇介丽, 杨枫, 刘桃桃, 李丹萍, 韩君蕊, 杨立洲. 血清miR-106b-5p、miR-760联合低剂量螺旋CT诊断早期肺癌的临床价值[J]. 国际肿瘤学杂志, 2024, 51(6): 321-325.
[2]	杨蜜, 别俊, 张加勇, 邓佳秀, 唐组阁, 卢俊. 局部晚期可切除食管癌新辅助治疗疗效及预后分析[J]. 国际肿瘤学杂志, 2024, 51(6): 332-337.
[3]	袁健, 黄燕华. Hp-IgG抗体联合血清DKK1、sB7-H3对早期胃癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(6): 338-343.
[4]	陈红健, 张素青. 血清miR-24-3p、H2AFX与肝癌患者临床病理特征及术后复发的关系研究[J]. 国际肿瘤学杂志, 2024, 51(6): 344-349.
[5]	郭泽浩, 张俊旺. PFDN及其亚基在肿瘤发生发展中的作用[J]. 国际肿瘤学杂志, 2024, 51(6): 350-353.
[6]	张百红, 岳红云. 新作用机制的抗肿瘤药物进展[J]. 国际肿瘤学杂志, 2024, 51(6): 354-358.
[7]	许凤琳, 吴刚. EBV在鼻咽癌肿瘤免疫微环境和免疫治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 359-363.
[8]	王盈, 刘楠, 郭兵. 抗体药物偶联物在转移性乳腺癌治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 364-369.
[9]	张蕊, 褚衍六. 基于FIT与肠道菌群的结直肠癌风险评估模型的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 370-375.
[10]	高凡, 王萍, 杜超, 褚衍六. 肠道菌群与结直肠癌非手术治疗的相关研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 376-381.
[11]	王丽, 刘志华, 杨伟洪, 蒋凤莲, 李全泳, 宋浩杰, 鞠文东. ROS1突变肺腺鳞癌合并脑梗死为主要表现的Trousseau综合征1例[J]. 国际肿瘤学杂志, 2024, 51(6): 382-384.
[12]	范志鹏, 余静, 胡静, 廖正凯, 徐禹, 欧阳雯, 谢丛华. 炎症标志物的变化趋势对一线接受免疫联合化疗的晚期非小细胞肺癌患者预后的预测价值[J]. 国际肿瘤学杂志, 2024, 51(5): 257-266.
[13]	刘静, 刘芹, 黄梅. 基于SMOTE算法的食管癌放化疗患者肺部感染的预后模型构建[J]. 国际肿瘤学杂志, 2024, 51(5): 267-273.
[14]	杨琳, 路宁, 温华, 张明鑫, 朱琳. 炎症负荷指数与胃癌临床关系研究[J]. 国际肿瘤学杂志, 2024, 51(5): 274-279.
[15]	王俊毅, 洪楷彬, 纪荣佳, 陈大朝. 癌结节对结直肠癌根治性切除术后肝转移的影响[J]. 国际肿瘤学杂志, 2024, 51(5): 280-285.