外泌体在胰腺癌诊断中的作用
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摘要
胰腺癌是死亡率极高的消化系统恶性肿瘤,外泌体是一种直径为30～200 nm,由多种细胞分泌释放到细胞外基质中的膜性囊泡结构,可以携带RNA、DNA、蛋白质和脂质等多种分子,并通过与靶细胞的结合介导细胞间的信息交流和调控细胞的生理功能。近年研究发现,外泌体不仅在胰腺癌的发生和发展中发挥重要作用,还有助于胰腺癌的早期诊断,并有望成为新的胰腺癌诊断标志物。阐述了外泌体在胰腺癌早期诊断中的研究进展。
Pancreatic cancer is a digestive system malignancy with high mortality. Exosomes are membranous vesicles with a diameter of 30-200 nm,which are released by various cells into the extracellular matrix. Exosomes can carry various molecules such as RNA,DNA,proteins,and lipids and bind to target cells to mediate the communication between cells and regulate the physiological function of cells. Recent studies have shown that exosomes play an important role in the development and progression of pancreatic cancer and can help with the early diagnosis of pancreatic cancer,and exosomes are expected to become a new biomarker for the diagnosis of pancreatic cancer. This article reviews the research advances in the role of exosomes in the early diagnosis of pancreatic cancer.
Pancreatic cancer is a digestive system malignancy with high mortality. Exosomes are membranous vesicles with a diameter of 30-200 nm,which are released by various cells into the extracellular matrix. Exosomes can carry various molecules such as RNA,DNA,proteins,and lipids and bind to target cells to mediate the communication between cells and regulate the physiological function of cells. Recent studies have shown that exosomes play an important role in the development and progression of pancreatic cancer and can help with the early diagnosis of pancreatic cancer,and exosomes are expected to become a new biomarker for the diagnosis of pancreatic cancer. This article reviews the research advances in the role of exosomes in the early diagnosis of pancreatic cancer.
引文
[1] TESFAYE AA,AZMI AS,PHILIP PA. miRNA and gene expression in pancreatic ductal adenocarcinoma[J]. Am J Pathol,2019,189(1):58-70.
[2] STROBEL O,NEOPTOLEMOS J,J?GER D,et al. Optimizing the outcomes of pancreatic cancer surgery[J]. Nat Rev Clin Oncol,2019,16(1):11-26.
[3] KAMISAWA T,WOOD LD,ITOI T,et al. Pancreatic cancer[J]. Lancet,2016,388(10039):73-85.
[4] de LIGUORI CARINO N,O'REILLY DA,SIRIWARDENA AK,et al. Irreversible Electroporation in pancreatic ductal adenocarcinoma:Is there a role in conjunction with conventional treatment[J]. Eur J Surg Oncol,2018,44(10):1486-1493.
[5] HERMANN PC,SAINZ B Jr. Pancreatic cancer stem cells:A state or an entity[J]. Semin Cancer Biol,2018,53:223-231.
[6] LIAO W,DU Y,ZHANG C,et al. Exosomes:The next generation of endogenous nanomaterials for advanced drug delivery and therapy[J]. Acta Biomater,2018,86:1-14.
[7] XU H,HAN H,SONG S,et al. Exosome-transmitted PSMA3and PSMA3-AS1 promotes proteasome inhibitors resistance in multiple myeloma[J]. Clin Cancer Res,2019,25(6):2363.
[8] MATHIEU M,MARTIN-JAULAR L,LAVIEU G,et al. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication[J]. Nat Cell Biol,2019,21(1):9-17.
[9] CONIGLIARO A,CICCHINI C. Exosome-mediated signaling in epithelial to mesenchymal transition and tumor progression[J]. J Clin Med,2018,8(1):e26.
[10] PAN BT,TENG K,WU C,et al. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes[J]. J Cell Biol,1985,101(3):942-948.
[11] ZHOU Y,REN H,DAI B,et al. Hepatocellular carcinomaderived exosomal miRNA-21 contributes to tumor progression by converting hepatocyte stellate cells to cancer-associated fibroblasts[J]. J Exp Clin Cancer Res,2018,37(1):324.
[12] KHARE D,OR R,RESNICK I,et al. Mesenchymal stromal cell-derived exosomes affect mRNA expression and function of B-lymphocytes[J]. Front Immunol,2018,9:3053.
[13] FENG M,ZHAO J,WANG L,et al. Upregulated expression of serum exosomal microRNAs as diagnostic biomarkers of lung adenocarcinoma[J]. Ann Clin Lab Sci,2018,48(6):712-718.
[14] MASSOUMI RL,HINES OJ,EIBL G,et al. Emerging evidence for the clinical relevance of pancreatic cancer exosomes[J].Pancreas,2019,48(1):1-8.
[15] MAZIVEYI M,DONG S,BARANWAL S,et al. Exosomes from Nischarin-expressing cells reduce breast cancer cell motility and tumor growth[J]. Cancer Res,2019.[Epub ahead of print]
[16] KAJIWARA C,FUMOTO K,KIMURA H,et al. p63-dependent Dickkopf3 expression promotes esophageal cancer cell proliferation via CKAP4[J]. Cancer Res,2018,78(21):6107-6120.
[17] CHEN L,YOU C,JIN X,et al. Cytoskeleton-associated protein 4 is a novel serodiagnostic marker for esophageal squamous-cell carcinoma[J]. Onco Targets Ther,2018,11:8221-8226.
[18] IGBINIGIE E,GUO F,JIANG SW,et al. Dkk1 involvement and its potential as a biomarker in pancreatic ductal adenocarcinoma[J]. Clin Chim Acta,2019,488:226-234.
[19] KIKUCHI A,FUMOTO K,KIMURA H. The Dickkopf1-cytoskeleton-associated protein 4 axis creates a novel signalling pathway and may represent a molecular target for cancer therapy[J]. Br J Pharmacol,2017,174(24):4651-4665.
[20] KIMURA H,YAMAMOTO H,HARADA T,et al. CKAP4,a DKK1receptor,is a biomarker in exosomes derived from pancreatic cancer and a molecular target for therapy[J]. Clin Cancer Res,2019,25(6):1936-1947.
[21] KITAGAWA T,TANIUCHI K,TSUBOI M,et al. Circulating pancreatic cancer exosomal RNAs for detection of pancreatic cancer[J]. Mol Oncol,2019,13(2):212-227.
[22] KINOSHITA-KAWADA M,HASEGAWA H,HONGU T,et al.A crucial role for Arf6 in the response of commissural axons to Slit[J]. Development,2019,146(3):dev172106.
[23] LIN JS,JEON JS,FAN Q,et al. ARF6 mediates nephrin tyrosine phosphorylation-induced podocyte cellular dynamics[J]. PLo S One,2017,12(9):e0184575.
[24] LI R,PENG C,ZHANG X,et al. Roles of Arf6 in cancer cell invasion,metastasis and proliferation[J]. Life Sci,2017,182:80-84.
[25] LIANG C,QIN Y,ZHANG B,et al. ARF6,induced by mutant Kras,promotes proliferation and Warburg effect in pancreatic cancer[J]. Cancer Lett,2017,388:303-311.
[26] MELO SA,LUECKE LB,KAHLERT C,et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer[J]. Nature,2015,523(7559):177-182.
[27] DIAMANDIS EP,PLEBANI M. Glypican-1 as a highly sensitive and specific pancreatic cancer biomarker[J]. Clin Chem Lab Med,2016,54(1):e1-e2.
[28] ZHOU CY,DONG YP,SUN X,et al. High levels of serum glypican-1 indicate poor prognosis in pancreatic ductal adenocarcinoma[J]. Cancer Med,2018,7(11):5525-5533.
[29] LAI X,WANG M,McELYEA SD,et al. A microRNA signature in circulating exosomes is superior to exosomal glypican-1levels for diagnosing pancreatic cancer[J]. Cancer Lett,2017,393:86-93.
[30] OSTEIKOETXEA X,BENKE M,RODRIGUEZ M,et al. Detection and proteomic characterization of extracellular vesicles in human pancreatic juice[J]. Biochem Biophys Res Commun,2018,499(1):37-43.
[31] ZHANG Y,HUANG S,LI P,et al. Pancreatic cancer-derived exosomes suppress the production of GIP and GLP-1 from STC-1 cells in vitro by down-regulating the PCSK1/3[J].Cancer Lett,2018,431:190-200.
[32] Pancreatic Cancer Committee of Chinese Anti-Cancer Association. Comprehensive guidelines for the diagnosis and treatment of pancreatic cancer(2018 version)[J]. J Clin Hepatol,2018,34(10):2109-2120.(in Chinese)中国抗癌协会胰腺癌专业委员会.胰腺癌综合诊治指南(2018版)[J].临床肝胆病杂志,2018,34(10):2109-2120.
[33] ZHAO X,REN Y,CUI N,et al. Identification of key microRNAs and their targets in exosomes of pancreatic cancer using bioinformatics analysis[J]. Medicine(Baltimore),2018,97(39):e12632.
[34] LI N,ZHAO X,YOU S. Identification of key regulators of pancreatic ductal adenocarcinoma using bioinformatics analysis of microarray data[J]. Medicine(Baltimore),2019,98(2):e14074.
[2] STROBEL O,NEOPTOLEMOS J,J?GER D,et al. Optimizing the outcomes of pancreatic cancer surgery[J]. Nat Rev Clin Oncol,2019,16(1):11-26.
[3] KAMISAWA T,WOOD LD,ITOI T,et al. Pancreatic cancer[J]. Lancet,2016,388(10039):73-85.
[4] de LIGUORI CARINO N,O'REILLY DA,SIRIWARDENA AK,et al. Irreversible Electroporation in pancreatic ductal adenocarcinoma:Is there a role in conjunction with conventional treatment[J]. Eur J Surg Oncol,2018,44(10):1486-1493.
[5] HERMANN PC,SAINZ B Jr. Pancreatic cancer stem cells:A state or an entity[J]. Semin Cancer Biol,2018,53:223-231.
[6] LIAO W,DU Y,ZHANG C,et al. Exosomes:The next generation of endogenous nanomaterials for advanced drug delivery and therapy[J]. Acta Biomater,2018,86:1-14.
[7] XU H,HAN H,SONG S,et al. Exosome-transmitted PSMA3and PSMA3-AS1 promotes proteasome inhibitors resistance in multiple myeloma[J]. Clin Cancer Res,2019,25(6):2363.
[8] MATHIEU M,MARTIN-JAULAR L,LAVIEU G,et al. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication[J]. Nat Cell Biol,2019,21(1):9-17.
[9] CONIGLIARO A,CICCHINI C. Exosome-mediated signaling in epithelial to mesenchymal transition and tumor progression[J]. J Clin Med,2018,8(1):e26.
[10] PAN BT,TENG K,WU C,et al. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes[J]. J Cell Biol,1985,101(3):942-948.
[11] ZHOU Y,REN H,DAI B,et al. Hepatocellular carcinomaderived exosomal miRNA-21 contributes to tumor progression by converting hepatocyte stellate cells to cancer-associated fibroblasts[J]. J Exp Clin Cancer Res,2018,37(1):324.
[12] KHARE D,OR R,RESNICK I,et al. Mesenchymal stromal cell-derived exosomes affect mRNA expression and function of B-lymphocytes[J]. Front Immunol,2018,9:3053.
[13] FENG M,ZHAO J,WANG L,et al. Upregulated expression of serum exosomal microRNAs as diagnostic biomarkers of lung adenocarcinoma[J]. Ann Clin Lab Sci,2018,48(6):712-718.
[14] MASSOUMI RL,HINES OJ,EIBL G,et al. Emerging evidence for the clinical relevance of pancreatic cancer exosomes[J].Pancreas,2019,48(1):1-8.
[15] MAZIVEYI M,DONG S,BARANWAL S,et al. Exosomes from Nischarin-expressing cells reduce breast cancer cell motility and tumor growth[J]. Cancer Res,2019.[Epub ahead of print]
[16] KAJIWARA C,FUMOTO K,KIMURA H,et al. p63-dependent Dickkopf3 expression promotes esophageal cancer cell proliferation via CKAP4[J]. Cancer Res,2018,78(21):6107-6120.
[17] CHEN L,YOU C,JIN X,et al. Cytoskeleton-associated protein 4 is a novel serodiagnostic marker for esophageal squamous-cell carcinoma[J]. Onco Targets Ther,2018,11:8221-8226.
[18] IGBINIGIE E,GUO F,JIANG SW,et al. Dkk1 involvement and its potential as a biomarker in pancreatic ductal adenocarcinoma[J]. Clin Chim Acta,2019,488:226-234.
[19] KIKUCHI A,FUMOTO K,KIMURA H. The Dickkopf1-cytoskeleton-associated protein 4 axis creates a novel signalling pathway and may represent a molecular target for cancer therapy[J]. Br J Pharmacol,2017,174(24):4651-4665.
[20] KIMURA H,YAMAMOTO H,HARADA T,et al. CKAP4,a DKK1receptor,is a biomarker in exosomes derived from pancreatic cancer and a molecular target for therapy[J]. Clin Cancer Res,2019,25(6):1936-1947.
[21] KITAGAWA T,TANIUCHI K,TSUBOI M,et al. Circulating pancreatic cancer exosomal RNAs for detection of pancreatic cancer[J]. Mol Oncol,2019,13(2):212-227.
[22] KINOSHITA-KAWADA M,HASEGAWA H,HONGU T,et al.A crucial role for Arf6 in the response of commissural axons to Slit[J]. Development,2019,146(3):dev172106.
[23] LIN JS,JEON JS,FAN Q,et al. ARF6 mediates nephrin tyrosine phosphorylation-induced podocyte cellular dynamics[J]. PLo S One,2017,12(9):e0184575.
[24] LI R,PENG C,ZHANG X,et al. Roles of Arf6 in cancer cell invasion,metastasis and proliferation[J]. Life Sci,2017,182:80-84.
[25] LIANG C,QIN Y,ZHANG B,et al. ARF6,induced by mutant Kras,promotes proliferation and Warburg effect in pancreatic cancer[J]. Cancer Lett,2017,388:303-311.
[26] MELO SA,LUECKE LB,KAHLERT C,et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer[J]. Nature,2015,523(7559):177-182.
[27] DIAMANDIS EP,PLEBANI M. Glypican-1 as a highly sensitive and specific pancreatic cancer biomarker[J]. Clin Chem Lab Med,2016,54(1):e1-e2.
[28] ZHOU CY,DONG YP,SUN X,et al. High levels of serum glypican-1 indicate poor prognosis in pancreatic ductal adenocarcinoma[J]. Cancer Med,2018,7(11):5525-5533.
[29] LAI X,WANG M,McELYEA SD,et al. A microRNA signature in circulating exosomes is superior to exosomal glypican-1levels for diagnosing pancreatic cancer[J]. Cancer Lett,2017,393:86-93.
[30] OSTEIKOETXEA X,BENKE M,RODRIGUEZ M,et al. Detection and proteomic characterization of extracellular vesicles in human pancreatic juice[J]. Biochem Biophys Res Commun,2018,499(1):37-43.
[31] ZHANG Y,HUANG S,LI P,et al. Pancreatic cancer-derived exosomes suppress the production of GIP and GLP-1 from STC-1 cells in vitro by down-regulating the PCSK1/3[J].Cancer Lett,2018,431:190-200.
[32] Pancreatic Cancer Committee of Chinese Anti-Cancer Association. Comprehensive guidelines for the diagnosis and treatment of pancreatic cancer(2018 version)[J]. J Clin Hepatol,2018,34(10):2109-2120.(in Chinese)中国抗癌协会胰腺癌专业委员会.胰腺癌综合诊治指南(2018版)[J].临床肝胆病杂志,2018,34(10):2109-2120.
[33] ZHAO X,REN Y,CUI N,et al. Identification of key microRNAs and their targets in exosomes of pancreatic cancer using bioinformatics analysis[J]. Medicine(Baltimore),2018,97(39):e12632.
[34] LI N,ZHAO X,YOU S. Identification of key regulators of pancreatic ductal adenocarcinoma using bioinformatics analysis of microarray data[J]. Medicine(Baltimore),2019,98(2):e14074.