肿瘤来源的外泌体在肿瘤进展中的作用及其诊疗意义
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摘要
外泌体是一种由细胞内多泡体与细胞膜融合产生的纳米级小囊泡。它们广泛分布在生物体血液、尿液、胸腹腔积液等几乎所有体液中。作为细胞间通讯和遗传物质的重要载体,外泌体可以通过各种生物活性分子,如细胞膜受体、蛋白质、信使RNA(messenger RNA,mRNA)和微小RNA(micro RNA,miRNA)的转移直接刺激靶细胞,从而发挥其生物学功能。从肿瘤细胞分泌的外泌体称为肿瘤来源的外泌体(tumor-derived exosome,TEX),除了具备外泌体的一般特征外更有其特殊性。研究TEX对肿瘤发生发展的影响将开辟全新的诊断和治疗肿瘤的新方法。
Exosomes are nanometer-sized vesicles produced by the fusion of multivesicular bodies and cell membranes which are widely distributed in almost all body fluids such as blood,urine,pleural and peritoneal effusions. As an important role of intercellular communication and genetic material carrier,exosomes play its biological function by stimulating target cells directly through the transfer of various bioactive molecules such as cell membrane receptors,proteins,messenger RNAs(mRNAs)and micro RNAs(miRNAs). Tumor-derived exosome(TEX)is a type of exosome secreted by tumor cells which not only has the general characteristics of exosomes but also has special features. Studying the effect of TEX will open up a whole new way to diagnosis and treatment of tumor.
Exosomes are nanometer-sized vesicles produced by the fusion of multivesicular bodies and cell membranes which are widely distributed in almost all body fluids such as blood,urine,pleural and peritoneal effusions. As an important role of intercellular communication and genetic material carrier,exosomes play its biological function by stimulating target cells directly through the transfer of various bioactive molecules such as cell membrane receptors,proteins,messenger RNAs(mRNAs)and micro RNAs(miRNAs). Tumor-derived exosome(TEX)is a type of exosome secreted by tumor cells which not only has the general characteristics of exosomes but also has special features. Studying the effect of TEX will open up a whole new way to diagnosis and treatment of tumor.
引文
[1]Cordonnier M,Chanteloup G,Isambert N,et al.Exosomes in cancer theranostic:Diamonds in the rough[J].Cell Adh Migr,2017,11(2):151-163
[2]Luhtala N,Aslanian A,Yates JR,et al.Secreted glioblastoma nanovesicles contain intracellular signaling proteins and active ras incorporated in a farnesylation-dependent manner[J].J Biol Chem,2017,292(2):611-628
[3]Kowal J,Tkach M,Thery C.Biogenesis and secretion of exosomes[J].Curr Opin Cell Biol,2014,29:116-125
[4]Zhang X,Yuan X,Shi H,et al.Exosomes in cancer:small particle,big player[J].J Hematol Oncol,2015,8(1):83
[5]Zhao L,Liu W,Xiao J,et al.The role of exosomes and“exosomal shuttle microRNA”in tumorigenesis and drug resistance[J].Cancer Lett,2015,356:339-346
[6]Colombo M,Raposo G,Thery C.Biogenesis,secretion,and intercellular interactions of exosomes and other extracellular vesicles[J].Annu Rev Cell Dev Biol,2014,30:255-289
[7]Frydrychowicz M,Kolecka BA,Madejczyk M,et al.Exosomes-structure,biogenesis and biological role in nonsmall-cell lung cancer[J].Scand J Immunol,2015,81(1):2-10
[8]Li Y,Zheng Q,Bao C,et al.Circular RNA is enriched and stable in exosomes:a promising biomarker for cancer diagnosis[J].Cell Res,2015,25(8):981-984
[9]Thakur BK,Zhang H,Becker A,et al.Double-stranded DNA in exosomes:a novel biomarker in cancer detection[J].Cell Res,2014,24(6):766-769
[10]Huang X,Yuan T,Liang M,et al.Exosomal miR-1290and miR-375 as prognostic markers in castration-resistant prostate cancer[J].Eur Urol,2015,67(1):33-41
[11]Riches A,Campbell E,Borger E,et al.Regulation of exosome release from mammary epithelial and breast cancer cells-a new regulatory pathway[J].Eur J Cancer,2014,50(5):1025-1034
[12]Matsumura T,Sugimachi K,Iinuma H,et al.Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer[J].Br J Cancer,2015,113(2):275-281
[13]魏玮,王艺,李霖,等.5-氟尿嘧啶耐药的晚期胃癌患者血清外泌体miRNA表达谱分析[J].肿瘤,2017,37(10):1047-1055
[14]Whiteside TL.Tumor-derived exosomes and their role in tumor-induced immune suppression[J].Vaccines(Basel),2016,4(4)
[15]Xu R,Greening DW,Rai A,et al.Highly-purified exosomes and shed microvesicles isolated from the colon cancer cell line LIM1863 by sequential ultrafiltration are biochemically and functionally distinct[J].Methods,2015,87(1):11-25
[16]Lai RC,Arslan F,Lee MM,et al.Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury[J].Stem Cell Res,2010,4(3):214-222
[17]胡国文,李青,牛鑫,等.旋转超滤:一种提取细胞外泌体的新方法[J].第二军医大学学报,2014,35(6):598-602
[18]陈加贵,邓敬桓,何敏.肝癌细胞外泌体的分离与鉴定[J].世界华人消化杂志,2016,24(5):737-743
[19]Meehan K,Vella LJ.The contribution of tumor-derived exosomes to the hallmarks of cancer[J].Crit Rev Clin Lab Sci,2016,53(2):121
[20]Wu L,Zhang X,Zhang B,et al.Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression[J].Tumor Biology,2016,37(9):12169
[21]Hong CS,Funk S,Muller L,et al.Isolation of biologically active and morphologically intact exosomes from plasma of patients with cancer[J].J Extracell Vesicles,2016,5:29289
[22]Huang X,Yuan T,Tschannen M,et al.Characterization of human plasma-derived exosomal RNAs by deep sequencing[J].BMC Genomics,2013,14:319
[23]李晓,刘玲英,柴家科,等.外泌体的生物学特性及临床应用的研究进展[J].解放军医学院学报,2015,36(10):1042-1044
[24]Arita T,Ichikawa D,Konishi H,et al.Tumor exosome-mediated promotion of adhesion to mesothelial cells in gastric cancer cells[J].Oncotarget,2016,7(35):56855-56863
[25]Shao Y,Shen Y,Chen T,et al.The functions and clinical applications of tumor-derived exosomes[J].Oncotarget,2016,7(37):60736-60751
[26]Khalyfa A,Almendros I,Gileles HA,et al.Circulating exosomes potentiate tumor malignant properties in a mouse model of chronic sleep fragmentation[J].Oncotarget,2016,7(34):54676-54690
[27]Gu H,Ji R,Zhang X,et al.Exosomes derived from human mesenchymal stem cells promote gastric cancer cell growth and migration via the activation of the Akt pathway[J].Mol Med Rep,2016,14(4):3452-3458
[28]杨子楠,魏继武.外泌体在肿瘤发展中的研究进展[J].肿瘤,2011,31(6):565-569
[29]de Vrij J,Maas Sl,Kwappenberg K,et al.Glioblastomaderived extracellular vesicles modify the phenotype of monocytic cells[J].Int J Cancer,2015,137(7):1630-1642
[30]Konstantinell A,Bruun JA,Olsen R,et al.Secretomic analysis of extracellular vesicles originating from polyomavirus-negative and polyomavirus-positive merkel cell carcinoma cell lines[J].Proteomics,2016,16(19):2587-2591
[31]Sanchez CA,Andahur EI,Valenzuela R,et al.Exosomes from bulk and stem cells from human prostate cancer have a differential microRNA content that contributes cooperatively over local and pre-metastatic niche[J].Oncotarget,2016,7(4):3993-4008
[32]Greening DW,Gopal SK,Mathias RA,et al.Emerging roles of exosomes during epithelial-mesenchymal transition and cancer progression[J].Semin Cell Dev Biol,2015,40(1):60-71
[33]Wu Y,Deng W,Mc Ginley EC,et al.Melanoma exosomes deliver a complex biological payload that upregulates PTPN11 to suppress T lymphocyte function[J].Pigment Cell Melanoma Res,2017,30(2):203-218
[34]Thakur BK,Zhang H,Becker A,et al.Double-stranded DNA in exosomes:a novel biomarker in cancer detection[J].Cell Res,2014,24(6):766-769
[35]Fang Y,Garnier D,Lee TH,et al.PML-RARa modulates the vascular signature of extracellular vesicles released by acute promyelocytic leukemia cells[J].Angiogenesis,2016,19(1):25-38
[36]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 Lett,2016,370(1):125-135
[37]Anderson JD,Johansson HJ,Graham CS,et al.Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-kappaB signaling[J].Stem Cells,2016,34(3):601-613
[38]Santos JC,Ribeiro ML,Sarian LO,et al.Exosomes-mediate microRNAs transfer in breast cancer chemoresistance regulation[J].Am J Cancer Res,2016,6(10):2129-2139
[39]Wang X,Xu C,Hua Y,et al.Exosomes play an important role in the process of psoralen reverse multidrug resistance of breast cancer[J].J Exp Clin Cancer Res,2016,35(1):186
[40]Ristorcelli E,Beraud E,Verrando P,et al.Human tumor nanoparticles induce apoptosis of pancreatic cancer cells[J].FASEB J,2008,22(9):3358-3369
[41]Greening DW,Gopal SK,Xu R,et al.Exosomes and their roles in immune regulation and cancer[J].Semin Cell Dev Biol,2015,40(1):72-81
[42]Ogata KH,Izumiya M,Kurioka D,et al.Circulating exosomal microRNAs as biomarkers of colon cancer[J].PLoS One,2014,9(4):e92921
[43]Que R,Ding G,Chen J,et al.Analysis of serum exosomal microRNAs and clinicopathologic features of patients with pancreatic adenocarcinoma[J].World J Surg Oncol,2013,11:219
[44]Grange C,Tapparo M,Collino F,et al.Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche[J].Cancer Res,2011,71(15):5346-5356
[45]Huang X,Yuan T,Liang M,et al.Exosomal miR-1290and miR-375 as prognostic markers in castration-resistant prostate cancer[J].Eur Urol,2015,67(1):33-41
[46]Ma J,Zhang Y,Tang K,et al.Reversing drug resistance of soft tumor-repopulating cells by tumor cell-derived chemotherapeutic microparticles[J].Cell Res,2016,26(6):713-727
[47]Wang Z,Chen JQ,Liu JL,et al.Exosomes in tumor microenvironment:novel transporters and biomarkers[J].JTransl Med,2016,14(1):297
[48]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
[49]Logozzi M,De MA,Lugini L,et al.High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients[J].PLoS One,2009,4(4):e5219
[2]Luhtala N,Aslanian A,Yates JR,et al.Secreted glioblastoma nanovesicles contain intracellular signaling proteins and active ras incorporated in a farnesylation-dependent manner[J].J Biol Chem,2017,292(2):611-628
[3]Kowal J,Tkach M,Thery C.Biogenesis and secretion of exosomes[J].Curr Opin Cell Biol,2014,29:116-125
[4]Zhang X,Yuan X,Shi H,et al.Exosomes in cancer:small particle,big player[J].J Hematol Oncol,2015,8(1):83
[5]Zhao L,Liu W,Xiao J,et al.The role of exosomes and“exosomal shuttle microRNA”in tumorigenesis and drug resistance[J].Cancer Lett,2015,356:339-346
[6]Colombo M,Raposo G,Thery C.Biogenesis,secretion,and intercellular interactions of exosomes and other extracellular vesicles[J].Annu Rev Cell Dev Biol,2014,30:255-289
[7]Frydrychowicz M,Kolecka BA,Madejczyk M,et al.Exosomes-structure,biogenesis and biological role in nonsmall-cell lung cancer[J].Scand J Immunol,2015,81(1):2-10
[8]Li Y,Zheng Q,Bao C,et al.Circular RNA is enriched and stable in exosomes:a promising biomarker for cancer diagnosis[J].Cell Res,2015,25(8):981-984
[9]Thakur BK,Zhang H,Becker A,et al.Double-stranded DNA in exosomes:a novel biomarker in cancer detection[J].Cell Res,2014,24(6):766-769
[10]Huang X,Yuan T,Liang M,et al.Exosomal miR-1290and miR-375 as prognostic markers in castration-resistant prostate cancer[J].Eur Urol,2015,67(1):33-41
[11]Riches A,Campbell E,Borger E,et al.Regulation of exosome release from mammary epithelial and breast cancer cells-a new regulatory pathway[J].Eur J Cancer,2014,50(5):1025-1034
[12]Matsumura T,Sugimachi K,Iinuma H,et al.Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer[J].Br J Cancer,2015,113(2):275-281
[13]魏玮,王艺,李霖,等.5-氟尿嘧啶耐药的晚期胃癌患者血清外泌体miRNA表达谱分析[J].肿瘤,2017,37(10):1047-1055
[14]Whiteside TL.Tumor-derived exosomes and their role in tumor-induced immune suppression[J].Vaccines(Basel),2016,4(4)
[15]Xu R,Greening DW,Rai A,et al.Highly-purified exosomes and shed microvesicles isolated from the colon cancer cell line LIM1863 by sequential ultrafiltration are biochemically and functionally distinct[J].Methods,2015,87(1):11-25
[16]Lai RC,Arslan F,Lee MM,et al.Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury[J].Stem Cell Res,2010,4(3):214-222
[17]胡国文,李青,牛鑫,等.旋转超滤:一种提取细胞外泌体的新方法[J].第二军医大学学报,2014,35(6):598-602
[18]陈加贵,邓敬桓,何敏.肝癌细胞外泌体的分离与鉴定[J].世界华人消化杂志,2016,24(5):737-743
[19]Meehan K,Vella LJ.The contribution of tumor-derived exosomes to the hallmarks of cancer[J].Crit Rev Clin Lab Sci,2016,53(2):121
[20]Wu L,Zhang X,Zhang B,et al.Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression[J].Tumor Biology,2016,37(9):12169
[21]Hong CS,Funk S,Muller L,et al.Isolation of biologically active and morphologically intact exosomes from plasma of patients with cancer[J].J Extracell Vesicles,2016,5:29289
[22]Huang X,Yuan T,Tschannen M,et al.Characterization of human plasma-derived exosomal RNAs by deep sequencing[J].BMC Genomics,2013,14:319
[23]李晓,刘玲英,柴家科,等.外泌体的生物学特性及临床应用的研究进展[J].解放军医学院学报,2015,36(10):1042-1044
[24]Arita T,Ichikawa D,Konishi H,et al.Tumor exosome-mediated promotion of adhesion to mesothelial cells in gastric cancer cells[J].Oncotarget,2016,7(35):56855-56863
[25]Shao Y,Shen Y,Chen T,et al.The functions and clinical applications of tumor-derived exosomes[J].Oncotarget,2016,7(37):60736-60751
[26]Khalyfa A,Almendros I,Gileles HA,et al.Circulating exosomes potentiate tumor malignant properties in a mouse model of chronic sleep fragmentation[J].Oncotarget,2016,7(34):54676-54690
[27]Gu H,Ji R,Zhang X,et al.Exosomes derived from human mesenchymal stem cells promote gastric cancer cell growth and migration via the activation of the Akt pathway[J].Mol Med Rep,2016,14(4):3452-3458
[28]杨子楠,魏继武.外泌体在肿瘤发展中的研究进展[J].肿瘤,2011,31(6):565-569
[29]de Vrij J,Maas Sl,Kwappenberg K,et al.Glioblastomaderived extracellular vesicles modify the phenotype of monocytic cells[J].Int J Cancer,2015,137(7):1630-1642
[30]Konstantinell A,Bruun JA,Olsen R,et al.Secretomic analysis of extracellular vesicles originating from polyomavirus-negative and polyomavirus-positive merkel cell carcinoma cell lines[J].Proteomics,2016,16(19):2587-2591
[31]Sanchez CA,Andahur EI,Valenzuela R,et al.Exosomes from bulk and stem cells from human prostate cancer have a differential microRNA content that contributes cooperatively over local and pre-metastatic niche[J].Oncotarget,2016,7(4):3993-4008
[32]Greening DW,Gopal SK,Mathias RA,et al.Emerging roles of exosomes during epithelial-mesenchymal transition and cancer progression[J].Semin Cell Dev Biol,2015,40(1):60-71
[33]Wu Y,Deng W,Mc Ginley EC,et al.Melanoma exosomes deliver a complex biological payload that upregulates PTPN11 to suppress T lymphocyte function[J].Pigment Cell Melanoma Res,2017,30(2):203-218
[34]Thakur BK,Zhang H,Becker A,et al.Double-stranded DNA in exosomes:a novel biomarker in cancer detection[J].Cell Res,2014,24(6):766-769
[35]Fang Y,Garnier D,Lee TH,et al.PML-RARa modulates the vascular signature of extracellular vesicles released by acute promyelocytic leukemia cells[J].Angiogenesis,2016,19(1):25-38
[36]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 Lett,2016,370(1):125-135
[37]Anderson JD,Johansson HJ,Graham CS,et al.Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-kappaB signaling[J].Stem Cells,2016,34(3):601-613
[38]Santos JC,Ribeiro ML,Sarian LO,et al.Exosomes-mediate microRNAs transfer in breast cancer chemoresistance regulation[J].Am J Cancer Res,2016,6(10):2129-2139
[39]Wang X,Xu C,Hua Y,et al.Exosomes play an important role in the process of psoralen reverse multidrug resistance of breast cancer[J].J Exp Clin Cancer Res,2016,35(1):186
[40]Ristorcelli E,Beraud E,Verrando P,et al.Human tumor nanoparticles induce apoptosis of pancreatic cancer cells[J].FASEB J,2008,22(9):3358-3369
[41]Greening DW,Gopal SK,Xu R,et al.Exosomes and their roles in immune regulation and cancer[J].Semin Cell Dev Biol,2015,40(1):72-81
[42]Ogata KH,Izumiya M,Kurioka D,et al.Circulating exosomal microRNAs as biomarkers of colon cancer[J].PLoS One,2014,9(4):e92921
[43]Que R,Ding G,Chen J,et al.Analysis of serum exosomal microRNAs and clinicopathologic features of patients with pancreatic adenocarcinoma[J].World J Surg Oncol,2013,11:219
[44]Grange C,Tapparo M,Collino F,et al.Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche[J].Cancer Res,2011,71(15):5346-5356
[45]Huang X,Yuan T,Liang M,et al.Exosomal miR-1290and miR-375 as prognostic markers in castration-resistant prostate cancer[J].Eur Urol,2015,67(1):33-41
[46]Ma J,Zhang Y,Tang K,et al.Reversing drug resistance of soft tumor-repopulating cells by tumor cell-derived chemotherapeutic microparticles[J].Cell Res,2016,26(6):713-727
[47]Wang Z,Chen JQ,Liu JL,et al.Exosomes in tumor microenvironment:novel transporters and biomarkers[J].JTransl Med,2016,14(1):297
[48]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
[49]Logozzi M,De MA,Lugini L,et al.High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients[J].PLoS One,2009,4(4):e5219
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