Proapoptotic function of integrin beta(3) in human hepatocellular carcinoma cells.
OBJECTIVE
This study evaluates the proapoptotic function of integrin beta(3) in human hepatocellular carcinoma (HCC).


METHODS
The expression of integrin beta(3) 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 beta(3) in SMMC-7721 human hepatoma cells overexpressing ITGB3 (gene coding integrin beta(3)) was determined through colony formation, serum starvation, and anoikis assay.


RESULTS
Compared with neighboring pathologically normal liver tissue, approximately 60% of the HCC specimens showed a significant down-regulated level of integrin beta(3) expression. Transient expression of integrin beta(3) in SMMC-7721 resulted 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-7721 with stable expression of integrin beta(3) in comparison with vector control transfectants. In addition, expression of fibrinogen and vitronectin, two native ligands for integrin alpha(v)beta(3) in liver, was inhibited, which was correlated with the decreased integrin beta(3) expression. Replenishing these ligands to the starved SMMC-7721 stable transfectants effectively restored the proapoptotic function of integrin beta(3).


CONCLUSIONS
Down-regulation of integrin beta(3) and its ligands in liver is related to the aggressive growth of HCC. Thus, reconstitution of integrin beta(3) in HCC may be a potential therapeutic approach to inhibit aggressive growth of liver cancer.
Wu
Yanhua
Y
State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai, P.R. China.
Zuo
Jie
J
Ji
Guoqing
G
Saiyin
Hexige
H
Liu
Xing
X
Yin
Feiyu
F
Cao
Ning
N
Wen
Yunfei
Y
Li
Jian Jian
JJ
Yu
Long
L
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D039661:Integrin beta3 / Q000502:physiology*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019096:Vitronectin / Q000378:metabolism
C061248:ITGB3 protein, human; D039661:Integrin beta3; D019096:Vitronectin; D005340:Fibrinogen