外泌体的功能及其在临床应用中的研究进展

doi:10.16431/j.cnki.1671-7236.2018.12.036

Abstract

Abstract:

Exosome is a nanoscale extracellular vesicle produced by fusion of intracellular multivesicular bodies with cell membranes.They are widely distributed in serum,urine,saliva and other biological fluids.As an important transfer vector for intercellular communication and genetic material,exosomes can directly stimulate target cells through receptor-mediated interactions or through the transfer of various biologically active molecules such as cell membrane receptors,proteins,mRNAs and miRNAs,thereby exerts its biological functions.The article mainly reviews the functions of proteins and miRNAs in exosomes and the clinical application of exosomes.The functions of proteins and miRNAs in exosomes include inducing immunity,presenting antigens,and participating in intercellular signaling under physiological conditions;Changing the tumor microenvironment under pathological conditions,promoting cancer cell proliferation,invasion,accelerating angiogenesis,and promoting cancer development;Certain viruses can package and integrate their components into exosomes to achieve intercellular transmission,or hijack exosomes for immune evasion.Exosome in the clinical should mainly introduce its biological markers for early diagnosis of various cancers such as lung cancer,breast cancer,pancreatic cancer and colorectal cancer,as well as high stability,high transport efficiency and strong targeting drug carrier is used for treatment.

Key words: exosome; protein; miRNA; disease diagnosis; drug carrier

CLC Number:

YANG Jinxin, WANG Haijun, ZHAO Yongkun, PEI Zhihua, SUN Mingjie, WANG Kai, HU Guixue. Research Progress on Exosome Function and Its Clinical Application[J]. , 2018, 45(12): 3608-3613.

References

[1] JOHNSTONE R M,ADAM M,HAMMOND J R,et al.Vesicle formation during reticulocyte maturation.Association of plasma membrane activities with released vesicles (exosomes)[J].Journal of Biological Chemistry,1987,262(19):9412-9420.
[2] RAPOSO G,NIJMAN H W,STOORVOGEL W,et al.B lymphocytes secrete antigen-presenting vesicles[J].Journal of Experimental Medicine,1996,183(3):1161-1172.
[3] MATHIVANAN S,FAHNER C J,REID G E,et al.ExoCarta 2012:Database of exosomal proteins,RNA and lipids[J].Nucleic Acids Research,2012,40(Database issue):D1241-1244.
[4] LI W,LI C,ZHOU T,et al.Role of exosomal proteins in cancer diagnosis[J].Molecular Cancer,2017,16(1):145.
[5] MATHIVANAN S,SIMPSON R J.ExoCarta:A compendium of exosomal proteins and RNA[J].Proteomics,2010,9(21):4997-5000.
[6] 吴金恩,丁军涛.外泌体生物学功能及应用研究进展[J].动物医学进展,2016,37(12):90-94. WU J N,DING J T.Research advances in biological function and application of exosomes[J].Bulletin of Animal Health,2016,37(12):90-94.(in Chinese)
[7] CLARK D J,FONDRIE W E,YANG A,et al.Triple SILAC quantitative proteomic analysis reveals differential abundance of cell signaling proteins between normal and lung cancer-derived exosomes[J].Journal of Proteomics,2016,133:161-169.
[8] FEDELE C,SINGH A,ZERLANKO B J,et al.The αvβ6 integrin is transferred intercellularly via exosomes[J].Journal of Biological Chemistry,2015,290(8):4545-4551.
[9] HOSHINO A,COSTA-SILVA B,SHEN T L,et al.Tumour exosome integrins determine organotropic metastasis[J].Nature,2015,527(7578):329-335.
[10] YU S,CAO H,SHEN B,et al.Tumor-derived exosomes in cancer progression and treatment failure[J].Oncotarget,2015,6(35):37151-37168.
[11] YANG W W,YANG L Q,ZHAO F,et al.Epiregulin promotes lung metastasis of salivary adenoid cystic carcinoma[J].Theranostics,2017,7(15):3700-3714.
[12] 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].Nature Cell Biology,2007,9(6):654-659.
[13] LIU Y,LUO F,WANG B,et al.STAT3-regulated exosomal miR-21 promotes angiogenesis and is involved in neoplastic processes of transformed human bronchial epithelial cells[J].Cancer Letters,2016,370(1):125-135.
[14] FANG T,LV H,LV G,et al.Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer[J].Nature Communications,2018,9(1):191.
[15] QU Z,WU J.Exosomal miR-665 as a novel minimally invasive biomarker for hepatocellular carcinoma diagnosis and prognosis[J].Oncotarget,2017,8(46):80666-80678.
[16] LI X J,REN Z J,TANG J H,et al.Exosomal micro-RNA miR-1246 promotes cell proliferation,invasion and drug resistance by targeting CCNG2 in breast cancer[J].Cellular Physiology and Biochemistry,2017,44(5):1741-1748.
[17] XU B,ZHANG Y,DU X F, et al.Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity[J].Cell Research,2017,27(7):882-897.
[18] YE Y,LI S L,MA Y Y,et al.Exosomal miR-141-3p regulates osteoblast activity to promote the osteoblastic metastasis of prostate cancer[J].Oncotarget,2017,8(55):94834-94849.
[19] 周昌娈,谭磊,丁铲.RNA病毒利用外泌体促进病毒感染的研究进展[J].微生物学通报,2017,44(12):2988-2996. ZHOU C L,TAN L,DING C.Advances of RNA virus increasing viral infection through the exosomes[J].Microbiology China,2017,44(12):2988-2996.(in Chinese)
[20] SATO Y,OCHIAI S,MURATA T,et al.Elimination of LMP1-expressing cells from a monolayer of gastric cancer AGS cells[J].Oncotarget,2017,8(24):39345-39355.
[21] JAWORSKI E,NARAYANAN A,VAN DUYNE R,et al.Human tlymphotropic virus type 1-infected cells secrete exosomes that contain Tax protein[J].Journal of Biological Chemistry,2014,289(32):22284-22305.
[22] SILVAS J A,POPOV V L,PAULUCCI H A,et al.Extracellular vesicles mediate receptor-independent transmission of novel tick-borne bunyavirus[J].Journal of Virology,2015,90(2):873-886.
[23] 张莉.外泌小体介导猪瘟病毒在ST细胞之间扩散的机制研究[D].长春:吉林农业大学,2016. ZHANG L.Exosome-mediated transmission of classical swine fever virus between ST cells[D].Changchun:Jilin Agricultural University,2016.(in Chinese)
[24] PLEET M L,MATHIESEN A,DEMARINO C,et al.Ebola VP40 in exosomes can cause immune cell dysfunction[J].Frontiers in Microbiology,2018,9(139):1765-1772.
[25] KOUWAKI T,FUKUSHIMA Y,DAITO T,et al.Extracellular vesicles including exosomes regulate innate immune responses to hepatitis B virus infec-tion[J].Frontiers in Immunology,2016,7:335-345.
[26] SANDFELD-PAULSEN B,JAKOBSEN K R.Exosomal proteins as diagnostic biomarkers in lung cancer[J].Journal of Thoracic Oncology,2016,11(10):1701-1710.
[27] ZHANG L,SHAN X,WANG J,et al.A three-microRNA signature for lung squamous cell carcinoma diagnosis in Chinese male patients[J].Oncotarget,2017,8(49):86897-86907.
[28] CHEN I H,XUE L,HSU C C,et al.Phosphoproteins in extracellular vesicles as candidate markers for breast cancer[J].Proceedings of the National Academy of Sciences of the United States of America,2017,114(12):3175-3180.
[29] MOON P G,LEE J E,CHO Y E,et al.Fibronectin on circulating extracellular vesicles as a liquid biopsy to detect breast cancer[J].Oncotarget,2016,7(26):40189-40199.
[30] MOON P G,LEE J E,CHOY E,et al.Identification of developmental endothelial locus-1 on circulating extracellular vesicles as a novel biomarker for early breast cancer detection[J].Clinical Cancer Research,2016,22(7):1757-1766.
[31] KIBRIA G,RAMOS E K,LEE K E,et al.A rapid,automated surface protein profiling of single circulating exosomes in human blood[J].Scientific Reports,2016,6:36502.
[32] HANNAFON B N,TRIGOSO Y D,CALLOWA C L,et al.Plasma exosome microRNAs are indicative of breast cancer[J].Breast Cancer Research,2016,18(1):90.
[33] MELO S A,LUECKE L B,KAHLERT C,et al.Glypican-1 identifies cancer exosomes and detects early pancreatic cancer[J].Nature,2015,523(7559):177-182.
[34] YAN S,DANG G,ZHANG X,et al.Downregulation of circulating exosomal miR-638 predicts poor prognosis in colon cancer patients[J].Oncotarget,2017,8(42):72220-72226.
[35] ZHOU X,WEN W,ZHU J,et al.A six-microRNA signature in plasma was identified as a potential biomarker in diagnosis of esophageal squamous cell carcinoma[J].Oncotarget,2017,8(21):34468-34480.
[36] LI S D,HOU X,QI H Z,et al.Exosomes:Provide naturally occurring endogenous nanocarriers for effective drug delivery strategies[J].Progress in Chemistry,2016,28(2-3):353-362.
[37] 赵安,郭利伟,陈爱萍,等.肿瘤外泌体:诊断与治疗[J].中国肿瘤,2017,26(3):190-195. ZHAO A,GUO L W,CHEN A P,et al.Exosome in tumor:Diagnosis and therapy[J].China Cancer,2017,26(3):190-195.(in Chinese)
[38] KHAN M,NICKOLOFF E,ABRAMOVA T,et al.Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction[J].Circulation Research,2015,117(1):52-64.
[39] SUN D,ZHUANG X,XIANG X,et al.A novel nanoparticle drug delivery system:The anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes[J].Molecular Therapy,2010,18(9):1606-1614.
[40] PASCUCCI L,COCCE V,BONOMI A,et al.Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth:A new approach for drug delivery[J].Journal of Controlled Release,2014,192(28):262-270.
[41] TIAN Y,LI S,SONG J,et al.A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy[J].Biomaterials,2014,35(7):2383-2390.

Research Progress on Exosome Function and Its Clinical Application

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	JIAO Linlin, CHENG Yuting, WU Qingguo, WU Shuang, WU Zhi, ZHU Shanyuan, QIAN Yingjuan. Prokaryotic Expression and Polyclonal Antibody Preparation of Duck Tembusu Virus Capsid Protein [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(6): 2395-2402.
[2]	SONG Yue, SU Shengjie, ZHANG Fan, BAI Fan, DAI Lingli, WANG Na, WANG Dawei, YANG Qianwen, ZHAO Shihua, ZHANG Yuemei. Prokaryotic Expression and Polyclonal Antibody Preparation of Mannheimia haemolytica Truncated Leukotoxin [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(6): 2479-2486.
[3]	WU Zhijuan, CHAI Zhixin, WANG Jikun, WANG Jiabo, ZHONG Jincheng, XIN Jinwei. Expression Analysis of Specific Matrix Metalloproteinases and Functionally Related Genes of Skeletal Muscles in Yak [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(5): 1774-1784.
[4]	ZHUO Na, ZHU Zhongwu, LI Jing, HU Shixiang, WANG Jianchang, LIN Hua, CHEN Chaolin, HAN Diangang, AI Jun, CHEN Peifu. Bioinformatics Analysis and Eukaryotic Expression of ORF2 Protein of Swine Hepatitis E Virus [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(5): 1959-1970.
[5]	ZHANG Fangyuan, LIN Yating, YANG Dawei, CHEN Hu, LI Guimei, SHAN Hu. Prokaryotic Expression of African Swine Fever Virus P30 Protein and Establishment of Indirect ELISA Detection Method [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(5): 2012-2022.
[6]	JIANG Haijun, WANG Dan, GUO Yu, WEI Li, HOU Lei, WANG Jing, ZHU Shanshan, LIU Jue. Fusion Expression and Immunogenicity of Recombinant Cap-flagellin Protein of Porcine Circovirus Type 3 [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(5): 2044-2052.
[7]	WANG Xueping, ZHANG Xiaojun, LI Xiaoyue, WANG Guodong, ZHANG Fuliang, SONG Yuwei, ZHANG Mingliang, MA Lei. Prokaryotic Expression of Hexon Protein of Highly Pathogenic Fowl Adenovirus Serotype 4 and Preparation of Polyclonal Antibodies [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(5): 2053-2060.
[8]	YU Xingang, YUAN Kaijian, MU Xuanru, WANG Hongcai, QI Nanshan, ZHANG Haoji. Research Progress on the Formation of Cyst Wall and Cyst Wall Proteins of Giardia [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(5): 2061-2068.
[9]	FAN Bingfeng, LI Wen, LIU Lixiang, ZHAO Xiangyuan, SHAO Jing, LIN Lefeng, SUN Huimin, ZHANG Xulin, XU Baozeng. Cloning and Bioinformatics Analysis of AANAT Gene in Mink [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(4): 1307-1318.
[10]	LI Zhijie, ZHAO Ying, MA Xin, WANG Meng, YU Sijiu, WANG Libin, PAN Yangyang. Research Progress on Isolation Methods and Main Reproductive Functions of Exosomes from Animal Follicular Fluid [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(4): 1480-1488.
[11]	WANG Wu, WANG Bi, BAI Yu, CHEN Qirong. Research Progress on Antibacterial Activity of Modified Lysozyme [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(3): 942-951.
[12]	FANG Qinyuan, FU Shaoyin, WANG Biao, HE Xiaolong, HE Jiangfeng, WANG Liwei, CHEN Xin, ZHANG Lin, WANG Daqing, MA Yuejun, ZHANG Liling, LIU Yongbin. Research Progress on Influencing Factors of Brown Fat Activity in Sheep [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(3): 1059-1067.
[13]	ZHANG Zhitao, LI Xianglong, KONG Lingli, LUO Yuxin, WANG Dongying. Prokaryotic Expression of Serine/Threonine Protein Phosphatase 2A in Fasciola gigantica and Expression Analysis at Different Stages [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(3): 1107-1117.
[14]	LI Huawei, GUO Kewei, WANG Xuying, ZHANG Xiaoyu, LU Ziwei, LI Xinfeng, MA Hui, HOU Wenjing. Eukaryotic Expression and Subcellular Localization of Nonstructural Protein 7 of Porcine Reproductive and Respiratory Syndrome Virus [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(3): 1160-1168.
[15]	MU Yijiao, YU Ruiming, ZHANG Liping, WANG Yonglu. Establishment and Application of ELISA for Detection of IgA Antibody Based on the Recombinant Full-length S2 Protein of Porcine Epidemic Diarrhea Virus Variant Strain [J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(3): 1185-1194.