外泌体在胰腺癌中的研究现状与进展
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摘要
外泌体是一种双层脂质膜连接囊泡样小体,存在于各种体液中,参与细胞及肿瘤微环境之间的物质运输和信号传递。外泌体含有多种生物活性分子,包括脂质、蛋白质、DNA、mRNA以及非编码RNA,可以通过这些活性分子影响肿瘤的发生和发展,甚至可以影响肿瘤的治疗。胰腺癌是一种常见的恶性肿瘤,侵袭性强,预后较差,死亡率高。胰腺癌来源的外泌体是胰腺肿瘤微环境中的重要组成部分,促使胰腺癌细胞成功逃避细胞凋亡的重要因素,并且可以促进肝脏转移微环境的形成。近年来,与胰腺癌相关的外泌体逐渐成为新的研究热点,研究发现外泌体有望成为早期胰腺癌筛查的新型生物学标志,并将为胰腺癌靶向治疗提供可行的技术基础。
Exosomes are lipid bilayer membrane-enclosed vesicles,confirmed in all bodily fluids. Exosomesare enriched in multiple bioactive molecule,including lipids,proteins,DNA,mRNA,as well asnon-coding RNA. Exosomes have emerged as an important tool for affecting tumorigenesis and tumor growth through these functional biomolecules,even as a potential drug delivery method. Pancreatic cancer,a common malignancy,poor prognosis and aggressive disease,is associated with a high mortality rate. Exosomes derived from pancreatic cancer are critical components in the tumor microenvironment. Exosomes have the capacity to protect pancreatic cancercells from apoptosis,and promote the formation of metastasis. Research on exosomes derived from pancreatic cancer and their functions is now a very exciting field. It is found that exosomes are expected to become a new biological marker of early pancreatic cancer,and will provide a viable technical basis for future targeted tumor therapy.
Exosomes are lipid bilayer membrane-enclosed vesicles,confirmed in all bodily fluids. Exosomesare enriched in multiple bioactive molecule,including lipids,proteins,DNA,mRNA,as well asnon-coding RNA. Exosomes have emerged as an important tool for affecting tumorigenesis and tumor growth through these functional biomolecules,even as a potential drug delivery method. Pancreatic cancer,a common malignancy,poor prognosis and aggressive disease,is associated with a high mortality rate. Exosomes derived from pancreatic cancer are critical components in the tumor microenvironment. Exosomes have the capacity to protect pancreatic cancercells from apoptosis,and promote the formation of metastasis. Research on exosomes derived from pancreatic cancer and their functions is now a very exciting field. It is found that exosomes are expected to become a new biological marker of early pancreatic cancer,and will provide a viable technical basis for future targeted tumor therapy.
引文
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[2]Winter JM,Cameron JL,Campbell KA,et al.1423 pancreaticoduodenectomies for pancreatic cancer:A single-institution experience[J].J Gastrointest Surg,2006,10(9):1199-1211.
[3]Milane L,Singh A,Mattheolabakis G,et al.Exosome mediated communication within the tumor microenvironment[J].J Control Release,2015,219:278-294.
[4]Abels ER,Breakefield XO.Introduction to extracellular vesicles:Biogenesis,RNA cargo selection,content,release,and uptake[J].Cell Mol Neurobiol,2016,36(3):301-312.
[5]Taylor DD,Gercel-Taylor C.Exosomes/microvesicles:mediators of cancer-associated immunosuppressive microenvironments[J].Semin Immunopathol,2011,33(5):441-454.
[6]Runz S,Keller S,Rupp C,et al.Malignant ascites-derived exosomes of ovarian carcinoma patients contain CD24 and EpCAM[J].Gynecol Oncol,2007,107(3):563-571.
[7]Andre F,Schartz NE,Movassagh M,et al.Malignant effusions and immunogenictumour-derived exosomes[J].Lancet,2002,360(9329):295-305.
[8]Ciravolo V,Huber V,Ghedini GC,et al.Potential role of HER2-overexpressing exosomes in countering trastuzumab-based therapy[J].J Cell Physiol,2012,227(2):658-667.
[9]Subra C,Laulagnier K,Perret B,et al.Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies[J].Biochimie,2007,89(2):205-212.
[10]Xu YF,Hannafon BN,Zhao YD,et al.Plasma exosome miR-196a and miR-1246 are potential indicators of localized pancreatic cancer[J].Oncotarget,2017,8(44):77028-77040.
[11]Lotvall J,Hill AF,Hochberg F,et al.Minimal experimental requirements for definition of extracellular vesicles and their functions:a position statement from the International Society for Extracellular Vesicles[J].J Extracell Vesicles,2014,3:26913.
[12]Takahasi K,Iinuma H,Wada K,et al.Usefulness of exosome-encapsulated microRNA-451a as a minimally invasive biomarker for prediction of recurrence and prognosis in pancreatic ductal adenocarcinoma[J].J Hepatobiliary Pancreat Sci,2018,25(2):155-161.
[13]Tsukamoto M,Iinuma H,Yagi T,et al.Circulating exosomal microRNA-21 as a biomarker in each tumor stage of colorectal cancer[J].Oncology,2017,92(6):360-370.
[14]Sessa F,Bonato M,Bisoni D,et al.Ki-ras and p53 gene mutations in pancreatic ductal carcinoma:a relationship with tumor phenotype and survival[J].Eur J Histochem,1998,42:67-76.
[15]Charrier A,Chen R,Chen L,et al.Connective tissue growth factor(CCN2)and microRNA-21 are components of a positive feedback loop in pancreatic stellate cells(PSC)during chronic pancreatitis and are exported in PSC-derived exosomes[J].J Cell Commun Signal,2014,8(2):147-156.
[16]Madhavan B,Yue S,Galli U,et al.Combined evaluation of a panel of protein and miRNA serum-exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity[J].Int JCancer,2015,136(11):2616-2627.
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[19]Frebourg T,Bercoff E,Manchon N,et al.The evaluation of CA 19-9 antigen level in the early detection of pancreatic cancer.Aprospective study of 866 patients[J].Cancer,1988,62(11):2287-2290.
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[22]Schey KL,Luther JM,Rose KL.Proteomics characterization of exosome cargo[J].Methods,2015,87:75-82.
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