Nitric oxide-dependent osteopontin expression induces metastatic behavior in HepG2 cells

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 implic...

Full description

Saved in:
Bibliographic Details
Published in:Digestive diseases and sciences 2005-07, Vol.50 (7), p.1288-1298
Main Authors: HONGTAO GUO, MARROQUIN, Carlos E, WAI, Philip Y, KUO, Paul C
Format: Article
Language:English
Subjects:
Biological and medical sciences
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - physiopathology
Carcinoma, Hepatocellular - secondary
Cell Adhesion
Cell Line, Tumor
Cell Movement
Feeding. Feeding behavior
Fundamental and applied biological sciences. Psychology
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Liver Neoplasms - physiopathology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Neoplasm Invasiveness
Nitric Oxide - metabolism
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type II
Osteopontin
Other diseases. Semiology
Promoter Regions, Genetic
RNA, Messenger - metabolism
Sialoglycoproteins - genetics
Sialoglycoproteins - metabolism
Transcription, Genetic
Tumors
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0163-2116
1573-2568
DOI:10.1007/s10620-005-2775-6