外泌体介导肿瘤发生发展进程的研究进展
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摘要
外泌体是一种直径为30～150 nm的双层膜结构的细胞外囊泡,能伴随多泡体与细胞膜的融合释放到细胞外,其中包覆了丰富的内容物,如蛋白质、脂质、核酸。近年来,人们发现外泌体作为一种信息传递方式,能够被受体细胞内化并传递内容物,从而参与各种生理病理过程。研究发现,肿瘤细胞来源的外泌体能够介导肿瘤的发生与发展,特别是影响肿瘤转移。因此,对外泌体的深入研究可为肿瘤的诊断与治疗提供新途径。
Exosomes are one type of extracellular vesicles about 30-150 nm in diameter. They can be secreted out of the cell with fusion of multivesicular bodies and cell membrane, which contain abundant contents such as proteins, lipids, nucleic acids. In recent years, it has been found that exosomes could transduct diverse biological signals among varied cells. They could be internalized by recipient cells, and further release the contents to recipient cells. Thereby, exosomes take part in various physiological and pathological processes. It was found that tumor cellderived exosomes could affect the occurrence and progression of cancer, especially metastasis. Therefore, exosomes might provide a new approach to the diagnosis and treatment of cancers.
Exosomes are one type of extracellular vesicles about 30-150 nm in diameter. They can be secreted out of the cell with fusion of multivesicular bodies and cell membrane, which contain abundant contents such as proteins, lipids, nucleic acids. In recent years, it has been found that exosomes could transduct diverse biological signals among varied cells. They could be internalized by recipient cells, and further release the contents to recipient cells. Thereby, exosomes take part in various physiological and pathological processes. It was found that tumor cellderived exosomes could affect the occurrence and progression of cancer, especially metastasis. Therefore, exosomes might provide a new approach to the diagnosis and treatment of cancers.
引文
[1]Tkach M,Théry C.Communication by extracellular vesicles:where we are and where we need to go.Cell,2016,164:1226-32
[2]Raposo G,Nijman HW,Stoorvogel W,et al.B lymphocytes secrete antigen-presenting vesicles.J Exp Med,1996,183:1161-72
[3]Hoshino A,Costa-Silva B,Shen TL,et al.Tumour exosome integrins determine organotropic metastasis.Nature,2015,527:329-35
[4]Peinado H,Ale?kovi?M,Lavotshkin S,et al.Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET.Nat Med,2012,18:883-91
[5]Van Niel G,D'Angelo G,Raposo G.Shedding light on the cell biology of extracellular vesicles.Nat Rev Mol Cell Biol,2018,19:213-28
[6]Subra C,Laulagnier K,Perret B,et al.Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies.Biochimie,2007,89:205-12
[7]Record M.Introduction to thematic review series on extracellular vesicles:a focus on the role of lipids.J Lipid Res,2018,59:1313-5
[8]Ying W,Riopel M,Bandyopadhyay G,et al.Adipose tissue macrophage-derived exosomal miRNA can modulate in vivo and in vitro insulin sensitivity.Cell,2017,171:372-84
[9]Thakur BK,Zhang H,Becker A,et al.Double-stranded DNA in exosomes:a novel biomarker in cancer detection.Cell Res,2014,24:766-9
[10]Melo SA,Sugimoto H,O'Connell JT,et al.Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis.Cancer Cell,2014,26:707-21
[11]Pavlyukov MS,Yu H,Bastola S,et al.Apoptotic cellderived extracellular vesicles promote malignancy of glioblastoma via intercellular transfer of splicing factors.Cancer Cell,2018,34:119-35
[12]Li S,Li Y,Chen B,et al.ExoRBase:a database of circRNA,lncRNA and mRNA in human blood exosomes.Nucleic Acids Res,2018,46:D106-12
[13]Kim DK,Lee J,Kim SR,et al.EVpedia:a community web portal for extracellular vesicles research.Bioinformatics,2015,31:933-9
[14]Raiborg C,Stenmark H.The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins.Nature,2009,458:445-52
[15]Lin MC,Chen SY,Tsai HM,et al.PGE2/EP4 signaling controls the transfer of the mammary stem cell state by lipid rafts in extracellular vesicles.Stem Cells,2017,35:425-44
[16]B?nfer S,Schneider D,Dewes J,et al.Molecular mechanism to recruit galectin-3 into multivesicular bodies for polarized exosomal secretion.Proc Natl Acad Sci USA,2018,115:E4396-405
[17]Ostrowski M,Carmo NB,Krumeich S,et al.Rab27a and Rab27b control different steps of the exosome secretion pathway.Nat Cell Biol,2010,12:19-30
[18]Villarroya-Beltri C,Baixauli F,Mittelbrunn M,et al.ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins.Nat Commun,2016,7:13588
[19]Hessvik NP,?verbye A,Brech A,et al.PIKfyve inhibition increases exosome release and induces secretory autophagy.Cell Mol Life Sci,2016,73:4717-37
[20]Hurwitz SN,Cheerathodi MR,Nkosi D,et al.Tetraspanin CD63 bridges autophagic and endosomal processes to regulate exosomal secretion and intracellular signaling of Epstein-Barr virus LMP1.J Virol,2018,92:e01969-17
[21]Villarroya-Beltri C,Gutiérrez-Vázquez C,Sánchez-Cabo F,et al.Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs.Nat Commun,2013,4:2980
[22]Cha DJ,Franklin JL,Dou Y,et al.KRAS-dependent sorting of miRNA to exosomes.Elife,2015,4:e07197
[23]Kajimoto T,Okada T,Miya S,et al.Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes.Nat Commun,2013,4:2712
[24]Li L,Li C,Wang S,et al.Exosomes derived from hypoxic oral squamous cell carcinoma cells deliver miR-21 to normoxic cells to elicit a prometastatic phenotype.Cancer Res,2016,76:1770-80
[25]Dorayappan KD,Wanner R,Wallbillich JJ,et al.Hypoxiainduced exosomes contribute to a more aggressive and chemoresistant ovarian cancer phenotype:a novel mechanism linking STAT3/Rab proteins.Oncogene,2018,37:3806-21
[26]Atienzar-Aroca S,Serrano-Heras G,Freire Valls A,et al.Role of retinal pigment epithelium-derived exosomes and autophagy in new blood vessel formation.J Cell Mol Med,2018,22:5244-56
[27]Heusermann W,Hean J,Trojer D,et al.Exosomes surf on filopodia to enter cells at endocytic hot spots,traffic within endosomes,and are targeted to the ER.J Cell Biol,2016,213:173-84
[28]Gonda A,Kabagwira J,Senthil GN,et al.Internalization of exosomes through receptor-mediated endocytosis.Mol Cancer Res,2019,17:337-47
[29]Feng D,Zhao WL,Ye YY,et al.Cellular internalization of exosomes occurs through phagocytosis.Traffic,2010,11:675-87
[30]Fitzner D,Schnaars M,van Rossum D,et al.Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis.J Cell Sci,2011,124:447-58
[31]Zomer A,Maynard C,Verweij FJ,et al.In vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior.Cell,2015,161:1046-57
[32]Thomou T,Mori MA,Dreyfuss JM,et al.Adipose-derived circulating miRNAs regulate gene expression in other tissues.Nature,2017,542:450-5
[33]Barker HE,Paget JT,Khan AA,et al.The tumour microenvironment after radiotherapy:mechanisms of resistance and recurrence.Nat Rev Cancer,2015,15:409-25
[34]Chen L,Feng Z,Yue H,et al.Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA.Nat Commun,2018,9:4585
[35]Zheng R,Du M,Wang X,et al.Exosome-transmitted long non-coding RNA PTENP1 suppresses bladder cancer progression.Mol Cancer,2018,17:143
[36]You Y,Shan Y,Chen J,et al.Matrix metalloproteinase13-containing exosomes promote nasopharyngeal carcinoma metastasis.Cancer Sci,2015,106:1669-77
[37]Jeppesen DK,Nawrocki A,Jensen SG,et al.Quantitative proteomics of fractionated membrane and lumen exosome proteins from isogenic metastatic and nonmetastatic bladder cancer cells reveal differential expression of EMTfactors.Proteomics,2014,14:699-712
[38]Chen L,Guo P,He Y,et al.HCC-derived exosomes elicit HCC progression and recurrence by epithelial-mesenchymal transition through MAPK/ERK signalling pathway.Cell Death Dis,2018,9:513
[39]Hardin H,Helein H,Meyer K,et al.Thyroid cancer stemlike cell exosomes:regulation of EMT via transfer of lncRNAs.Lab Invest,2018,98:1133-42
[40]Chen X,Chen RX,Wei WS,et al.PRMT5 circular RNApromotes metastasis of urothelial carcinoma of the bladder through sponging miR-30c to induce epithelial-mesenchymal transition.Clin Cancer Res,2018,24:6319-30
[41]Hood JL,San RS,Wickline SA.Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis.Cancer Res,2011,71:3792-801
[42]Costa-Silva B,Aiello NM,Ocean AJ,et al.Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver.Nat Cell Biol,2015,17:816-26
[43]Novo D,Heath N,Mitchell L,et al.Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels.Nat Commun,2018,9:5069
[44]Plebanek MP,Angeloni NL,Vinokour E,et al.Premetastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche.Nat Commun,2017,8:1319
[45]Lin XJ,Fang JH,Yang XJ,et al.Hepatocellular carcinoma cell-secreted exosomal microRNA-210 promotes angiogenesis in vitro and in vivo.Mol Ther Nucleic Acids,2018,11:243-52
[46]Kucharzewska P,Christianson HC,Welch JE,et al.Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development.Proc Natl Acad Sci USA,2013,110:7312-7
[47]You Y,Shan Y,Chen J,et al.Matrix metalloproteinase13-containing exosomes promote nasopharyngeal carcinoma metastasis.Cancer Sci,2015,106:1669-77
[48]Baroni S,Romero-Cordoba S,Plantamura I,et al.Exosome-mediated delivery of miR-9 induces cancerassociated fibroblast-like properties in human breast fibroblasts.Cell Death Dis,2016,7:e2312
[49]Yan W,Wu X,Zhou W,et al.Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells.Nat Cell Biol,2018,20:597-609
[50]Whiteside TL.Immune modulation of T-cell and NK(natural killer)cell activities by TEXs(tumour-derived exosomes).Biochem Soc Trans,2013,41:245-51
[51]Cooks T,Pateras IS,Jenkins LM,et al.Mutant p53cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246.Nat Commun,2018,9:771
[52]Zhou J,Li X,Wu X,et al.Exosomes released from tumorassociated macrophages transfer miRNAs that induce a Treg/Th17 cell imbalance in epithelial ovarian cancer.Cancer Immunol Res,2018,6:1578-92
[53]Battke C,Ruiss R,Welsch U,et al.Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC.Cancer Immunol Immunother,2011,60:639-48
[54]Kahlert C,Melo SA,Protopopov A,et al.Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer.J Biol Chem,2014,289:3869-75
[55]Bhagirath D,Yang TL,Bucay N,et al.MicroRNA-1246 is an exosomal biomarker for aggressive prostate cancer.Cancer Res,2018,78:1833-44
[56]Chen G,Huang AC,Zhang W,et al.Exosomal PD-L1contributes to immunosuppression and is associated with anti-PD-1 response.Nature,2018,560:382-6
[57]Baietti MF,Zhang Z,Mortier E,et al.Syndecan-synteninALIX regulates the biogenesis of exosomes.Nat Cell Biol,2012,14:677-85
[58]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.Cancer Res,2012,72:4920-30
[59]Grassart A,Cheng AT,Hong SH,et al.Actin and dynamin2 dynamics and interplay during clathrinmediated endocytosis.J Cell Biol,2014,205:721-35
[60]Tian Y,Li S,Song J,et al.A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy.Biomaterials,2014,35:2383-90
[61]Kamerkar S,LeBleu VS,Sugimoto H,et al.Exosomes facilitate therapeutic targeting of oncogenic Kras in pancreatic cancer.Nature,2017,546:498-503
[62]Sansone P,Savini C,Kurelac I,et al.Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer.Proc Natl Acad Sci USA,2017,114:E9066-75
[63]Mutschelknaus L,Azimzadeh O,Heider T,et al.Radiation alters the cargo of exosomes released from squamous head and neck cancer cells to promote migration of recipient cells.Sci Rep,2017,7:12423
[64]Shao H,Im H,Castro CM,et al.New technologies for analysis of extracellular vesicles.Chem Rev,2018,118:1917-50
[65]Lewis JM,Vyas AD,Qiu Y,et al.Integrated analysis of exosomal protein biomarkers on alternating current electrokinetic chips enables rapid detection of pancreatic cancer in patient blood.ACS Nano,2018,12:3311-20
[2]Raposo G,Nijman HW,Stoorvogel W,et al.B lymphocytes secrete antigen-presenting vesicles.J Exp Med,1996,183:1161-72
[3]Hoshino A,Costa-Silva B,Shen TL,et al.Tumour exosome integrins determine organotropic metastasis.Nature,2015,527:329-35
[4]Peinado H,Ale?kovi?M,Lavotshkin S,et al.Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET.Nat Med,2012,18:883-91
[5]Van Niel G,D'Angelo G,Raposo G.Shedding light on the cell biology of extracellular vesicles.Nat Rev Mol Cell Biol,2018,19:213-28
[6]Subra C,Laulagnier K,Perret B,et al.Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies.Biochimie,2007,89:205-12
[7]Record M.Introduction to thematic review series on extracellular vesicles:a focus on the role of lipids.J Lipid Res,2018,59:1313-5
[8]Ying W,Riopel M,Bandyopadhyay G,et al.Adipose tissue macrophage-derived exosomal miRNA can modulate in vivo and in vitro insulin sensitivity.Cell,2017,171:372-84
[9]Thakur BK,Zhang H,Becker A,et al.Double-stranded DNA in exosomes:a novel biomarker in cancer detection.Cell Res,2014,24:766-9
[10]Melo SA,Sugimoto H,O'Connell JT,et al.Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis.Cancer Cell,2014,26:707-21
[11]Pavlyukov MS,Yu H,Bastola S,et al.Apoptotic cellderived extracellular vesicles promote malignancy of glioblastoma via intercellular transfer of splicing factors.Cancer Cell,2018,34:119-35
[12]Li S,Li Y,Chen B,et al.ExoRBase:a database of circRNA,lncRNA and mRNA in human blood exosomes.Nucleic Acids Res,2018,46:D106-12
[13]Kim DK,Lee J,Kim SR,et al.EVpedia:a community web portal for extracellular vesicles research.Bioinformatics,2015,31:933-9
[14]Raiborg C,Stenmark H.The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins.Nature,2009,458:445-52
[15]Lin MC,Chen SY,Tsai HM,et al.PGE2/EP4 signaling controls the transfer of the mammary stem cell state by lipid rafts in extracellular vesicles.Stem Cells,2017,35:425-44
[16]B?nfer S,Schneider D,Dewes J,et al.Molecular mechanism to recruit galectin-3 into multivesicular bodies for polarized exosomal secretion.Proc Natl Acad Sci USA,2018,115:E4396-405
[17]Ostrowski M,Carmo NB,Krumeich S,et al.Rab27a and Rab27b control different steps of the exosome secretion pathway.Nat Cell Biol,2010,12:19-30
[18]Villarroya-Beltri C,Baixauli F,Mittelbrunn M,et al.ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins.Nat Commun,2016,7:13588
[19]Hessvik NP,?verbye A,Brech A,et al.PIKfyve inhibition increases exosome release and induces secretory autophagy.Cell Mol Life Sci,2016,73:4717-37
[20]Hurwitz SN,Cheerathodi MR,Nkosi D,et al.Tetraspanin CD63 bridges autophagic and endosomal processes to regulate exosomal secretion and intracellular signaling of Epstein-Barr virus LMP1.J Virol,2018,92:e01969-17
[21]Villarroya-Beltri C,Gutiérrez-Vázquez C,Sánchez-Cabo F,et al.Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs.Nat Commun,2013,4:2980
[22]Cha DJ,Franklin JL,Dou Y,et al.KRAS-dependent sorting of miRNA to exosomes.Elife,2015,4:e07197
[23]Kajimoto T,Okada T,Miya S,et al.Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes.Nat Commun,2013,4:2712
[24]Li L,Li C,Wang S,et al.Exosomes derived from hypoxic oral squamous cell carcinoma cells deliver miR-21 to normoxic cells to elicit a prometastatic phenotype.Cancer Res,2016,76:1770-80
[25]Dorayappan KD,Wanner R,Wallbillich JJ,et al.Hypoxiainduced exosomes contribute to a more aggressive and chemoresistant ovarian cancer phenotype:a novel mechanism linking STAT3/Rab proteins.Oncogene,2018,37:3806-21
[26]Atienzar-Aroca S,Serrano-Heras G,Freire Valls A,et al.Role of retinal pigment epithelium-derived exosomes and autophagy in new blood vessel formation.J Cell Mol Med,2018,22:5244-56
[27]Heusermann W,Hean J,Trojer D,et al.Exosomes surf on filopodia to enter cells at endocytic hot spots,traffic within endosomes,and are targeted to the ER.J Cell Biol,2016,213:173-84
[28]Gonda A,Kabagwira J,Senthil GN,et al.Internalization of exosomes through receptor-mediated endocytosis.Mol Cancer Res,2019,17:337-47
[29]Feng D,Zhao WL,Ye YY,et al.Cellular internalization of exosomes occurs through phagocytosis.Traffic,2010,11:675-87
[30]Fitzner D,Schnaars M,van Rossum D,et al.Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis.J Cell Sci,2011,124:447-58
[31]Zomer A,Maynard C,Verweij FJ,et al.In vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior.Cell,2015,161:1046-57
[32]Thomou T,Mori MA,Dreyfuss JM,et al.Adipose-derived circulating miRNAs regulate gene expression in other tissues.Nature,2017,542:450-5
[33]Barker HE,Paget JT,Khan AA,et al.The tumour microenvironment after radiotherapy:mechanisms of resistance and recurrence.Nat Rev Cancer,2015,15:409-25
[34]Chen L,Feng Z,Yue H,et al.Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA.Nat Commun,2018,9:4585
[35]Zheng R,Du M,Wang X,et al.Exosome-transmitted long non-coding RNA PTENP1 suppresses bladder cancer progression.Mol Cancer,2018,17:143
[36]You Y,Shan Y,Chen J,et al.Matrix metalloproteinase13-containing exosomes promote nasopharyngeal carcinoma metastasis.Cancer Sci,2015,106:1669-77
[37]Jeppesen DK,Nawrocki A,Jensen SG,et al.Quantitative proteomics of fractionated membrane and lumen exosome proteins from isogenic metastatic and nonmetastatic bladder cancer cells reveal differential expression of EMTfactors.Proteomics,2014,14:699-712
[38]Chen L,Guo P,He Y,et al.HCC-derived exosomes elicit HCC progression and recurrence by epithelial-mesenchymal transition through MAPK/ERK signalling pathway.Cell Death Dis,2018,9:513
[39]Hardin H,Helein H,Meyer K,et al.Thyroid cancer stemlike cell exosomes:regulation of EMT via transfer of lncRNAs.Lab Invest,2018,98:1133-42
[40]Chen X,Chen RX,Wei WS,et al.PRMT5 circular RNApromotes metastasis of urothelial carcinoma of the bladder through sponging miR-30c to induce epithelial-mesenchymal transition.Clin Cancer Res,2018,24:6319-30
[41]Hood JL,San RS,Wickline SA.Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis.Cancer Res,2011,71:3792-801
[42]Costa-Silva B,Aiello NM,Ocean AJ,et al.Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver.Nat Cell Biol,2015,17:816-26
[43]Novo D,Heath N,Mitchell L,et al.Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels.Nat Commun,2018,9:5069
[44]Plebanek MP,Angeloni NL,Vinokour E,et al.Premetastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche.Nat Commun,2017,8:1319
[45]Lin XJ,Fang JH,Yang XJ,et al.Hepatocellular carcinoma cell-secreted exosomal microRNA-210 promotes angiogenesis in vitro and in vivo.Mol Ther Nucleic Acids,2018,11:243-52
[46]Kucharzewska P,Christianson HC,Welch JE,et al.Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development.Proc Natl Acad Sci USA,2013,110:7312-7
[47]You Y,Shan Y,Chen J,et al.Matrix metalloproteinase13-containing exosomes promote nasopharyngeal carcinoma metastasis.Cancer Sci,2015,106:1669-77
[48]Baroni S,Romero-Cordoba S,Plantamura I,et al.Exosome-mediated delivery of miR-9 induces cancerassociated fibroblast-like properties in human breast fibroblasts.Cell Death Dis,2016,7:e2312
[49]Yan W,Wu X,Zhou W,et al.Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells.Nat Cell Biol,2018,20:597-609
[50]Whiteside TL.Immune modulation of T-cell and NK(natural killer)cell activities by TEXs(tumour-derived exosomes).Biochem Soc Trans,2013,41:245-51
[51]Cooks T,Pateras IS,Jenkins LM,et al.Mutant p53cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246.Nat Commun,2018,9:771
[52]Zhou J,Li X,Wu X,et al.Exosomes released from tumorassociated macrophages transfer miRNAs that induce a Treg/Th17 cell imbalance in epithelial ovarian cancer.Cancer Immunol Res,2018,6:1578-92
[53]Battke C,Ruiss R,Welsch U,et al.Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC.Cancer Immunol Immunother,2011,60:639-48
[54]Kahlert C,Melo SA,Protopopov A,et al.Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer.J Biol Chem,2014,289:3869-75
[55]Bhagirath D,Yang TL,Bucay N,et al.MicroRNA-1246 is an exosomal biomarker for aggressive prostate cancer.Cancer Res,2018,78:1833-44
[56]Chen G,Huang AC,Zhang W,et al.Exosomal PD-L1contributes to immunosuppression and is associated with anti-PD-1 response.Nature,2018,560:382-6
[57]Baietti MF,Zhang Z,Mortier E,et al.Syndecan-synteninALIX regulates the biogenesis of exosomes.Nat Cell Biol,2012,14:677-85
[58]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.Cancer Res,2012,72:4920-30
[59]Grassart A,Cheng AT,Hong SH,et al.Actin and dynamin2 dynamics and interplay during clathrinmediated endocytosis.J Cell Biol,2014,205:721-35
[60]Tian Y,Li S,Song J,et al.A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy.Biomaterials,2014,35:2383-90
[61]Kamerkar S,LeBleu VS,Sugimoto H,et al.Exosomes facilitate therapeutic targeting of oncogenic Kras in pancreatic cancer.Nature,2017,546:498-503
[62]Sansone P,Savini C,Kurelac I,et al.Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer.Proc Natl Acad Sci USA,2017,114:E9066-75
[63]Mutschelknaus L,Azimzadeh O,Heider T,et al.Radiation alters the cargo of exosomes released from squamous head and neck cancer cells to promote migration of recipient cells.Sci Rep,2017,7:12423
[64]Shao H,Im H,Castro CM,et al.New technologies for analysis of extracellular vesicles.Chem Rev,2018,118:1917-50
[65]Lewis JM,Vyas AD,Qiu Y,et al.Integrated analysis of exosomal protein biomarkers on alternating current electrokinetic chips enables rapid detection of pancreatic cancer in patient blood.ACS Nano,2018,12:3311-20