Nitric oxide-dependent osteopontin expression induces metastatic behavior in HepG2 cells.
Journal Article (Journal Article)
Our objective was to delineate the role of nitric oxide (NO) in osteopontin (OPN)-associated metastatic properties in HepG2 cells. OPN is the major phosphoprotein secreted by malignant cells in patients with advanced metastatic cancer, is frequently overexpressed in human tumors, and has been implicated as a key mediator of tumor cell metastasis. OPN is significantly overexpressed in hepatocellular cancer (HCC) and correlates with capsular infiltration and behavior. In addition, significantly increased inducible nitric oxide synthase (iNOS) and NO expression are found in HCC. In archived human samples of normal, cirrhotic, and HCC livers, we demonstrate that iNOS and OPN protein are strongly coexpressed in hepatoma cells. In the setting of cirrhosis, hepatocytes express iNOS, but not OPN. Further in vitro studies performed with HepG2 hepatocellular cancer cells demonstrate that exogenous NO transcriptionally upregulates OPN expression. Enhanced expression of OPN in this setting is associated with increased in vitro cell adhesion and invasion. These data suggest that NO enhances HCC expression of OPN and, as a result, conveys a metastatic phenotype.
Full Text
Duke Authors
Cited Authors
- Guo, H; Marroquin, CE; Wai, PY; Kuo, PC
Published Date
- July 2005
Published In
Volume / Issue
- 50 / 7
Start / End Page
- 1288 - 1298
PubMed ID
- 16047475
International Standard Serial Number (ISSN)
- 0163-2116
Digital Object Identifier (DOI)
- 10.1007/s10620-005-2775-6
Language
- eng
Conference Location
- United States