Proapoptotic function of integrin beta(3) in human hepatocellular carcinoma cells.
Proapoptotic function of integrin beta(3) in human hepatocellular carcinoma cells.
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DOI：
10.1158/1078-0432.ccr-08-1028
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Yu L
中科院分区：
文献类型：
--
作者：
Wu Y;Zuo J;Ji G;Saiyin H;Liu X;Yin F;Cao N;Wen Y;Li JJ;Yu L
本研究旨在探讨整合素β3在人肝细胞癌（HCC）中的促凋亡作用。采用实时荧光定量PCR和Western blot方法检测67例肝癌组织及相应癌旁组织中整合素β3的表达。通过集落形成、血清饥饿和失巢凋亡实验，研究了整合素β3在过表达ITGB 3（整合素β3基因）的SMMC-7721人肝癌细胞中的促凋亡作用。与邻近正常肝组织相比，约60%的肝癌组织中整合素β3表达水平显著下调。整合素β3的瞬时表达可导致SMMC-7721细胞凋亡水平的增加和集落形成的抑制。与载体对照转染子相比，整合素β3稳定表达的SMMC-7721中血清/配体剥夺对细胞生长的抑制作用和失巢凋亡的发生率显着增加。此外，肝脏中整合素αvβ3的天然配体纤维蛋白原和玻连蛋白的表达也受到抑制，这与整合素β3的表达减少有关。向饥饿的SMMC-7721稳定转染子补充这些配体有效地恢复了整合素β3的促凋亡功能。肝组织中整合素β3及其配体表达下调与肝癌侵袭性生长有关。因此，整合素β3在HCC中的重建可能是抑制肝癌侵袭性生长的潜在治疗方法。
This study evaluates the proapoptotic function of integrin β3 in human hepatocellular carcinoma (HCC). The expression of integrin β3 in 67 HCC specimens paired with corresponding neighboring nontumorous tissue was studied by quantitative real-time PCR and Western blot. The proapoptotic function of integrin β3 in SMMC-7721 human hepatoma cells overexpressing ITGB3 (gene coding integrin β3) was determined through colony formation, serum starvation, and anoikis assay. Compared with neighboring pathologically normal liver tissue, ~60% of the HCC specimens showed a significantdown-regulated level of integrin β3 expression. Transient expression of integrin β3 in SMMC-7721resulted in an enhanced level of apoptosis and suppression of colony formation. Cell growth inhibition on serum/ligand deprivation and incidences of anoikis were remarkably increased in SMMC-7721with stable expression of integrin β3 in comparison with vector control transfectants. In addition, expression of fibrinogen and vitronectin, two native ligands for integrin αvβ3 in liver, was inhibited, which was correlated with the decreased integrin β3 expression. Replenishing these ligands to the starved SMMC-7721 stable transfectants effectively restored the proapoptotic function of integrin β3. Down-regulation of integrin β3 and its ligands in liver is related to the aggressive growth of HCC. Thus, reconstitution of integrin β3 in HCC may be a potential therapeutic approach to inhibit aggressive growth of liver cancer.