胰腺癌缺氧微环境的生物学作用

张雨; 江建新

doi:10.3969/j.issn.1001-5256.2020.03.054

胰腺癌缺氧微环境的生物学作用

DOI: 10.3969/j.issn.1001-5256.2020.03.054

张雨,
江建新

武汉大学人民医院肝胆外科

基金项目:

国家自然科学基金(8187101814)；

详细信息

中图分类号: R735.9
计量
- 文章访问数: 1066
- HTML全文浏览量: 29
- PDF下载量: 216
- 被引次数: 0
出版历程
- 收稿日期: 2019-10-10
- 出版日期: 2020-03-20

Biological role of hypoxic microenvironment in pancreatic cancer

Department of Hepatobiliary Surgery,Renmin Hospital of Wuhan University

Research funding:

摘要

摘要: 癌细胞生长迅速及中心血供不足导致的缺氧是肿瘤微环境特性之一,在胰腺癌中尤为突出。越来越多的研究显示,缺氧与胰腺癌的血管新生、代谢重建、肿瘤增殖及早期浸润转移密切相关,并通过分泌多种活性因子介导肿瘤免疫逃避。此外,耐药作为胰腺癌治愈率低的关键因素,也与缺氧相关。缺氧与胰腺癌的发生发展密不可分,并依赖于缺氧诱导因子发挥作用。对缺氧微环境与胰腺癌的关系进行了总结,并探讨相关信号通路激活与分子机制,以期为胰腺癌缺氧微环境靶向治疗提供线索。
- 胰腺肿瘤 /
- 缺氧 /
- 肿瘤微环境
Abstract: Hypoxia caused by rapid growth of cancer cells and insufficient central blood supply is one of the characteristics of tumor microenvironment,especially in pancreatic cancer. An increasing number of studies have shown that hypoxia is closely associated with angiogenesis,metabolic reprogramming,tumor proliferation,and early invasion and metastasis of pancreatic cancer and can mediate tumor immune evasion by secreting a variety of active factors. In addition,as a key factor for the low cure rate of pancreatic cancer,drug resistance is also associated with hypoxia. Hypoxia is closely associated with the development and progression of pancreatic cancer and depends on hypoxia-inducible factor. This article summarizes the association between hypoxic microenvironment and pancreatic cancer and discusses the activation of related signaling pathways and molecular mechanisms,in order to provide clues for targeted therapy for hopoxic microenvironment in pancreatic cancer.
- pancreatic neoplasms /
- hypoxia /
- tumor microenvironment

HTML全文

参考文献(35)

[1] SIEGEL RL,MILLER KD,JEMAL A. Cancer statistics,2019[J]. CA Cancer J Clin,2019,69(1):7-34.

[2] ZHENG RS,SUN KX,ZHANG SW,et al. Report of cancer epidemiology in China,2015[J]. Chin J Oncol,2019,41(1):19-28.(in Chinese)郑荣寿，孙可欣，张思维，等．2015年中国恶性肿瘤流行情况分析[J]．中华肿瘤杂志，2019,41(1):19-28.

[3] PAGET S. The distribution of secondary growths in cancer of the breast[J]. Lancet,1889,133:571-573.

[4] DOUGAN SK. The pancreatic cancer microenvironment[J].Cancer J,2017,23(6):321-325.

[5] WU CZ,HAN X,WANG Y. Tumor microenvironment and its regulation of immunity,vessels,metabolism,and nutrition[J/CD]. Electronic J Metab Nutr Cancer,2016,3(4):220-223.(in Chinese)吴朝真，韩晓，王悦．肿瘤微环境及其调节的免疫、血管及代谢营养[J/CD]．肿瘤代谢与营养电子杂志，2016,3(4):220-223.

[6] REN B,CUI M,YANG G,et al. Tumor microenvironment participates in metastasis of pancreatic cancer[J]. Mol Cancer,2018,17(1):108.

[7] ZHAI ZS,ZHANG HW. Hypoxic microenvironment in inhibiting tumor metastasis[J]. J Chin Pract Diagn Ther,2019,33(2):191-193.(in Chinese)翟振胜，张宏伟．缺氧微环境调控肿瘤转移研究进展[J]．中华实用诊断与治疗杂志，2019,33(2):191-193.

[8] MANOOCHEHRI KHOSHINANI H,AFSHAR S,NAJAFI R. Hypoxia:A double-edged sword in cancer therapy[J]. Cancer Invest,2016,34(10):536-545.

[9] ERKAN M,KURTOGLU M,KLEEFF J. The role of hypoxia in pancreatic cancer:A potential therapeutic target?[J]. Expert Rev Gastroenterol Hepatol,2016,10(3):301-316.

[10] YE L,TANG ZG. Research progress of hypoxia inducible factor in pancreatic cancer[J]. Med Recapitulate,2019,25(10):1949-1953.(in Chinese)叶林，汤志刚．缺氧诱导因子在胰腺癌中的研究进展[J]．医学综述，2019,25(10):1949-1953.

[11] HUANG RQ. Influence on hypoxia induced factor-1 for invasive metastasis of tumor[J]. Lingnan Mod Clin Surg,2011,11(3):232-235.(in Chinese)黄锐钦．缺氧诱导因子-1α对肿瘤侵袭转移的影响[J]．岭南现代临床外科，2011,11(3):232-235.

[12] WANG M,CHEN MY,GUO XJ,et al. Expression and significance of HIF-1αand HIF-2αin pancreatic cancer[J]. J Huazhong Univ Sci Technolog Med Sci,2015,35(6):874-879.

[13] ZHOU X,GUO X,CHEN M,et al. HIF-3αpromotes metastatic phenotypes in pancreatic cancer by transcriptional regulation of the Rho C-ROCK1 signaling pathway[J]. Mol Cancer Res,2018,16(1):124-134.

[14] MAO M,LI Q,QIU YL,et al. Production of reactive oxygen species in the mitochondria and its mechanism of action in regulating hypoxic pulmonary hypertension[J]. J Harbin Med Univ,2014,48(6):525-527,531.(in Chinese)毛敏，李倩，邱艳丽，等．线粒体活性氧的产生及调节缺氧性肺动脉高压作用机制[J]．哈尔滨医科大学学报，2014,48(6):525-527,531.

[15] HOSEIN AN,BEG MS. Pancreatic cancer metabolism:Molecular mechanisms and clinical applications[J]. Curr Oncol Rep,2018,20(7):56.

[16] SUNAMI Y,REBELO A,KLEEFF J,et al. Lipid metabolism and lipid droplets in pancreatic cancer and stellate cells[J].Cancers(Basel),2017,10(1):e3.

[17] ICARD P,SHULMAN S,FARHAT D,et al. How the Warburg effect supports aggressiveness and drug resistance of cancer cells?[J]. Drug Resist Updat,2018,38:1-11.

[18] YANG YH,ZHANG YX,GUI Y,et al. Research advances in the role of autophagy and perineural invasion in pancreatic cancer[J]. J Clin Hepatol,2018,34(11):2475-2479.(in Chinese)杨延辉，张玉祥，桂洋，等．胰腺癌与自噬、神经浸润的关系[J]．临床肝胆病杂志，2018,34(11):2475-2479.

[19] DANIEL SK,SULLIVAN KM,LABADIE KP,et al. Hypoxia as a barrier to immunotherapy in pancreatic adenocarcinoma[J].Clin Transl Med,2019,8(1):10.

[20] ZHANG GF,CAI JQ,CUI TJ,et al. Effects of CD40 pathway on the biological behavior of pancreatic cancer cells[J]. Chin J Clin Pharmacol Ther,2018,23(7):755-760.(in Chinese)张桂枫，蔡加琴，崔同建，等．CD40调节胰腺癌细胞生物学行为的研究[J]．中国临床药理学与治疗学，2018,23(7):755-760.

[21] JEIN YK,PARK SG,CHOI IW,et al. Cancer cell-associated cytoplasmic B7-H4 is induced by hypoxia through hypoxiainducible factor-1αand promotes cancer cell proliferation[J]. Biochem Biophys Res Commun,2015,459(2):277-283.

[22] BARBU A,LEJONKLOU MH,SKOGSEID B. Progranulin stimulates proliferation of mouse pancreatic islet cells and is overexpressed in the endocrine pancreatic tissue of an MEN1mouse model[J]. Pancreas,2016,45(4):533-540.

[23] LI Y,ZHANG X,YANG J,et al. Methylation of BNIP3 in pancreatic cancer inhibits the induction of mitochondrial-mediated tumor cell apoptosis[J]. Oncotarget,2017,8(38):63208-63222.

[24] HARASHIMA N,TAKENAGA K,AKIMOTO M,et al. HIF-2αdictates the susceptibility of pancreatic cancer cells to TRAIL by regulating survivin expression[J]. Oncotarget,2017,8(26):42887-42900.

[25] WANG P,WAN WW,XIONG SL,et al. Cancer stem-like cells can be induced through dedifferentiation under hypoxic conditions in glioma,hepatoma and lung cancer[J]. Cell Death Discov,2017,3:16105.

[26] ZHENG G,LIU JS,ZHI RH. Expression and clinical significance of CTGF,VEGF and HIF-1αin pancreatic carcinoma[J]. China Med Herald,2011,8(13):31-33.(in Chinese)郑刚，刘建生，智仁厚．结缔组织生长因子、血管内皮生长因子、缺氧诱导因子-1α在胰腺癌中的表达及临床意义[J]．中国医药导报，2011,8(13):31-33.

[27] YANG J,ZHU DM,ZHOU XG,et al. HIF-2αpromotes the formation of vasculogenic mimicry in pancreatic cancer by regulating the binding of Twist1 to the VE-cadherin promoter[J]. Oncotarget,2017,8(29):47801-47815.

[28] WANG SG,SHAN YZ,ZHOU LM,et al. Effect of HIF-1αon the epithelial mesenchymal transition and invasion and migration of pancreatic cancer cells under hypoxic condition[J].Mod Oncol,2016,24(11):1704-1709.(in Chinese)王时光，单远洲，周联明，等．缺氧微环境下HIF-1α对胰腺癌细胞上皮间质转化及侵袭迁移的影响[J]．现代肿瘤医学，2016,24(11):1704-1709.

[29] WU Y,LIU DF,ZHANG C,et al. Hypoxic stellate cells of pancreatic cancer stroma induce cancer cell migration and invasion via CCL7/CCR5 axis[J]. Acta Univ Med Nanjing,2017,37(5):521-525,543.(in Chinese)吴飏，刘东方，张纯，等．缺氧微环境中胰腺星状细胞通过CCL7/CCR5轴促进胰腺癌侵袭[J]．南京医科大学学报，2017,37(5):521-525,543.

[30] ZHANG Q,LOU Y,ZHANG J,et al. Hypoxia-inducible factor-2αpromotes tumor progression and has crosstalk with Wnt/β-catenin signaling in pancreatic cancer[J]. Mol Cancer,2017,16(1):119.

[31] LIU WZ,HU Y,ZHANG C. Research progress in tumor microenvironment and immunotherapy of pancreatic cancer[J].Chin J Immunol,2018,34(12):1901-1906.(in Chinese)刘文增，胡渊，张彩．胰腺癌的肿瘤微环境及其免疫治疗研究进展[J]．中国免疫学杂志，2018,34(12):1901-1906.

[32] GRASSO C,JANCEN G,GIOVANNRTTI E. Drug resistance in pancreatic cancer:Impact of altered energy metabolism[J].Crit Rev Oncol Hematol,2017,114:139-152.

[33] GAIANIGO N,MELISI D,CARBONE C. EMT and treatment resistance in pancreatic cancer[J]. Cancers(Basel),2017,9(9):e122.

[34] HE X,WANG J,WEI W,et al. Hypoxia regulates ABCG2 activity through the activivation of ERK1/2/HIF-1αand contributes to chemoresistance in pancreatic cancer cells[J]. Cancer Biol Ther,2016,17(2):188-198.

[35] LUO G,XIA X,WANG X,et al. miR-301a plays a pivotal role in hypoxia-induced gemcitabine resistance in pancreatic cancer[J]. Exp Cell Res,2018,369(1):120-128.

施引文献

资源附件(0)

访问统计