Osteopontin-dependent CD44v6 expression and cell adhesion in HepG2 cells

被引：64

作者：

Gao, CJ ^{[1
]}

Guo, HT ^{[1
]}

Downey, L ^{[1
]}

Marroquin, C ^{[1
]}

Wei, JP ^{[1
]}

Kuo, PC ^{[1
]}

机构：

[1] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA

来源：

CARCINOGENESIS | 2003年 / 24卷 / 12期

关键词：

D O I：

10.1093/carcin/bgg139

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The interaction of osteopontin (OPN) with CD44 and alpha(v)beta(3)-integrin has been implicated in numerous signal transduction pathways that may promote cancer metastasis. CD44v6 is a splice variant of CD44 which has been identified as a marker of cancer progression. In this study, immortalized liver carcinoma cells (HepG2) were used to examine the effect of OPN on two isoforms of CD44: CD44 standard (CD44 s) and CD44v6. Western blots demonstrated that OPN up-regulated plasma membrane CD44v6 protein expression in a concentration- and time-dependent fashion. CD44v6 levels returned to control levels when OPN-alpha(v)beta(3)-integrin binding was blocked by an RGD peptide or tyrosine kinase activity was inhibited. OPN significantly increased CD44v6 protein synthesis, while simultaneously decreasing protein degradation. Steady-state mRNA levels of both CD44s and CD44v6 were unaltered in the presence of OPN stimulation. OPN increased HepG2 in vitro adhesion to hyaluronate (HA); excess soluble HA extinguished OPN-mediated HepG2 adhesion, indicating CD44 dependence. In conclusion, OPN binds to the alpha(v)beta(3)-integrin to increase plasma membrane CD44v6 expression and augment in vitro adhesion to HA. This may contribute to the mechanism by which OPN enhances metastatic behavior in hepatocellular cancer cells.

引用

页码：1871 / 1878

页数：8

共 24 条

[1]

Agrawal D, 2002, J NATL CANCER I, V94, P513

[2]

Barbour AP, 2003, CANCER RES, V63, P887

[3] Osteopontin deficiency produces osteoclast dysfunction due to reduced CD44 surface expression [J].