血管内皮生长因子受体与肝细胞癌侵袭转移的关系  

Expression of vascular endothelial growth factor receptors and invasion and metastasis of hepatocellular carcinoma

作　　者：李存娣 曹伟娅 王健 LI Cundi;CAO Weiya;WANG Jian(Department of Etiology and Immunology,Medical College of Anhui University of Science and Technology,Huainan,Anhui 232001,China)

机构地区：[1]安徽理工大学医学院病原生物学教研室

出　　处：《临床肝胆病杂志》2019年第7期1616-1620,共5页Journal of Clinical Hepatology

基　　金：安徽省教育厅重大自然科学研究项目(KJ2016SD20);中国煤炭工业协会科研项目(MTKJ 2015-333);安徽省自然科学基金(1308085MH148);安徽省2015年高等教育振兴计划项目重大教学改革研究项目(2015zdjy068)

摘　　要：血管内皮生长因子受体(VEGFR)含3种受体酪氨酸激酶(RTK)超家族成员和2种非RTK超家族成员,其与配体以非一一对应形式相互结合,通过细胞表面受体内化作用介导Raf1→MAP2K1/2→ERK1/2等多条信号传导通路,引起肝癌细胞增殖和血管、淋巴管生成。VEGFR在肝癌患者局部癌灶高表达,是介导肝细胞癌恶性增生、侵袭转移的关键因素,与患者无进展生存期呈负相关。基质金属蛋白酶-9、热休克蛋白90β可上调VEGFR促进肝癌细胞增殖转移,而miR-203a、miR-378a、miR-199a-3p等可下调VEGFR表达抑制肝癌细胞浸润。基于VEGFR靶向药物治疗可诱导肝癌细胞凋亡,阻断肿瘤血管新生,延缓患者病情进展。Vascular endothelial growth factor receptors (VEGFRs) consist of three receptor tyrosine kinase (RTK) superfamily members and two non-RTK superfamily members and bind to the ligand in a non-one-to-one way. VEGFRs mediate various signaling pathways such as Raf1→MAP2K1/2→ERK1/2 through cell surface receptor internalization and thus promote the proliferation of hepatocellular carcinoma cells, angiogenesis, and lymphangiogenesis. VEGFRs can be highly expressed in local cancerous lesions of liver cancer patients, which is a key factor mediating malignant proliferation, invasion, and metastasis of hepatocellular carcinoma, and the expression of VEGFRs is negatively correlated with progression-free survival. Matrix metalloproteinase-9 and heat shock protein 90β can upregulate VEGFRs to promote the proliferation and metastasis of hepatoma cells, while miR-203a, miR-378a, and miR-199a-3p can downregulate VEGFR expression and inhibit hepatoma cell infiltration. Targeted drug therapy based on VEGFR can induce the apoptosis of hepatoma cells, block tumor angiogenesis, and delay disease progression.

关 键 词：受体 血管内皮生长因子 癌 肝细胞 肿瘤形成过程 

分 类 号：R735.7[医药卫生—肿瘤]