基质金属蛋白酶家族调控肝细胞癌发展及其机制研究的进展  

Research progress on matrix metalloproteinases regulating development of hepatocellular carcinoma and its mechanisms

作　　者：谢亮[1,2] 郭灏[1] 何洪宇 周国俊 冷政伟 严德辉[1] 徐明清[2] XIE Liang;GUO Hao;HE Hongyu;ZHOU Guojun;LENG Zhengwei;YAN Dehui;XU Mingqing(The Second Department of Hepatobiliary Surgery,Affiliated Hospital of North Sichuan Medical College,Nanchong,Sichuan 630700,P.R.China;Division of Liver Surgery,Department of General Surgery,West China Hospital,Sichuan University,Chengdu 610041,P.R.China)

机构地区：[1]川北医学院附属医院肝胆外二科,四川南充630700 [2]四川大学华西医院普外科肝脏外科病房,成都610041

出　　处：《中国普外基础与临床杂志》2024年第5期625-633,共9页Chinese Journal of Bases and Clinics In General Surgery

基　　金：四川省科技厅重点课题(项目编号:2021YFSY0009);川北医学院校级科研课题(项目编号:CBY18-A-YB17);川北医学院附属医院科研发展计划项目(项目编号:2021ZD018);川北医学院附属医院高层次人才科研启动基金项目(项目编号:2023-2GC018)。

摘　　要：目的了解基质金属蛋白酶(matrix metalloproteinases,MMPs)家族调控肝细胞癌(hepatocellular carcinoma,HCC)发展及其机制研究的进展,以期为HCC的基础研究及临床的诊断和治疗提供借鉴和帮助。方法对近年来国内外关于MMPs调控HCC发生、发展及其机制研究的相关文献进行综述。结果HCC的细胞外基质微环境决定了肿瘤细胞的侵袭性和转移程度;上皮间质转化过程中细胞外基质降解及重塑是HCC侵袭、转移的主要因素,而MMPs家族中大多数成员的非正常表达均可导致细胞外基质降解、细胞侵袭和附着并显著加速上皮间质转化进程,从而促进HCC的侵袭及转移。目前与HCC发展相关研究较多的MMPs包括MMP-1、2、3、7、9、12、13、14,MMP-8、10、11、15、16、20、21、26、28与HCC发展相关的研究还相对较有限,而MMP-17、19、23、24、25、27与HCC发展确切相关的研究尚未检索到。结论MMPs家族(尤其是MMP-2、3、7、9、10、12)在HCC的增殖、侵袭、转移等进展过程中起十分重要的作用。进一步探索MMPs家族所有成员与HCC发展可能存在的内在联系,对预测HCC转移潜力和预后情况及开发新的或改进HCC当前靶向抗癌治疗至关重要。Objective To understand the research progress of the matrix metalloproteinases(MMPs)family in regulating the development of hepatocellular carcinoma(HCC)and its mechanism,in order to provide a reference for the basic research and clinical diagnosis and treatment of HCC.Method The relevant literature on the regulation of HCC occurrence,development,and mechanisms by MMPs both domestically and internationally in recent years was reviewed.Results The extracellular matrix(ECM)microenvironment of HCC cells determined the invasiveness and degree of metastasis of tumor cells.The degradation and remodeling of ECM during epithelial mesenchymal transition(EMT)were the main factors contributing to the invasion and metastasis of HCC.The abnormal expression of most members of the MMPs family could lead to ECM breakdown,cell invasion and attachment,and markedly accelerate the process of EMT,thereby promoting the invasion and metastasis of HCC cells.At present,there were many MMPs related to the development of HCC,including MMP-1,2,3,7,9,12,13,14.The relevant research on the relation between MMP-8,10,11,15,16,20,21,26 or 28 and the development of HCC was relatively limited,while the exact research on the relationship between the MMP-17,19,23,24,25 or 27 and HCC development had not been retrievaled.Conclusions The MMPs family members(especially MMP-2,3,7,9,10,12)play a crucial role in the progression of HCC,including proliferation,invasion,and metastasis.Further exploration of the potential intrinsic relation between all members of the MMPs family members and the development of HCC is crucial for predicting HCC metastasis potentiality and prognosis,as well as developing new or improved targeted anti-cancer therapies for HCC.

关 键 词：金属基质蛋白酶 肝细胞癌 细胞外基质 上皮间质转化 

分 类 号：R73[医药卫生—肿瘤]