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.
Abstract
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.
基金项目
四川省科技厅重点项目(2021YFSY0009)
川北医学院校级科研项目(CBY18-A-YB17)
川北医学院附属医院科研发展计划(2021ZD018)
川北医学院附属医院高层次人才科研启动基金(2023-2GC018)
NETL
NSTL
万方数据