含血小板反应蛋白18型基序的解聚素样金属蛋白酶在肝细胞癌中的表达及其生物学功能

Expression and biological functions of human A disintegrin and metalloproteinase with thrombospondin motifs 18 in human hepatocellular carcinoma

目的探讨含血小板反应蛋白18型基序的解聚素样金属蛋白酶(ADAMTS18)在肝细胞癌(HCC)中的表达及其对HCC细胞迁移、侵袭功能的影响。方法免疫组化染色法检测50对HCC及癌旁组织中ADAMTS18表达。分析ADAMTS18表达与患者临床特征的相关性。通过转染ADAMTS18过表达质粒提高Huh-7细胞内ADAMTS18的表达水平,Transwell小室模型检测过表达ADAMTS18对Huh-7细胞迁移和侵袭的影响,蛋白质免疫印迹检测过表达ADAMTS18对Huh-7细胞内蛋白激酶B(AKT)磷酸化及E-cadherin表达的影响。结果ADAMTS18在HCC组织中的表达水平显著降低(P=0.003);ADAMTS18低表达与HCC血管侵犯(P=0.018)及TNM分期(P=0.038)密切相关。过表达ADAMTS18抑制Huh-7细胞迁移(P=0.038)、侵袭(P=0.027)和AKT磷酸化(P=0.047),但促进了E-cadherin表达(P=0.032)。结论ADAMTS18低表达与HCC恶性临床特征密切相关,ADAMTS18可能通过抑制AKT的磷酸化而发挥抗HCC细胞迁移侵袭作用。

Objective To investigate the expression of human A disintegrin and metalloproteinase with thrombospondin motif 18(ADAMTS18)in human hepatocellular carcinoma(HCC)and its impact on migration and invasion of HCC cells.Methods The expression of ADAMTS18 in 50 paired HCC and matched tumor adjacent tissues were detected by immunohistochemistry.The relationship between ADAMTS18 expression and clinical features was analyzed.ADAMTS18 was up-regulated in Huh-7 cells by overexpression of plasmids.The impacts of overexpression of ADAMTS18 on Huh-7 cell migration and invasion,phosphorylated AKT and expression of E-cadherin in Huh-7 cells were explored by Transwell chamber assays,Western blot assays,respectively.Results The expression of ADAMTS18 was decreased in HCC tissues(P=0.003).Low expression of ADAMTS18 was associated with vascular infiltration(P=0.018)and TNM staging(P=0.038).Overexpression of ADAMTS18 inhibited migration of Huh-7 cells(P=0.038),invasion(P=0.027),and AKT phosphorylation(P=0.047),but increased E-cadherin expression(P=0.032).Conclusion Lower expression of ADAMTS18 is closely associated with features of HCC malignancy,ADAMTS18 in HCC tissues may suppress cell migration and invasion through inhibiting AKT phosphorylation.