Caveolin-1 is associated with VCAM-1 dependent adhesion of gastric cancer cells to endothelial cells.

Abstract

BACKGROUND/AIMS:

Cell adhesion molecules play a critical role in the invasion and metastasis of a variety of human tumors. Abnormal expression of VCAM-1 has been demonstrated to correlate with the malignant progression of gastric tumors, but the molecular mechanism underlying the VCAM-1-dependent metastasis has been rarely investigated. To explore the role for tumor cell-expressing adhesion molecules in the carcinoma-endothelium adhesion, we analyzed expression status of adhesion molecules in gastric cancer cells and its association with tumor cell capability of endothelial adhesion.

METHODS:

Endothelial adhesion ability of gastric tumor cells was tested using calcein AM staining assay. Expression of cell surface proteins was determined by Western blot, flow cytometry, and immunofluorescence assays. RNAi-mediated knockdown of gene expression and neutralization with specific antibodies were utilized for functional analysis.

RESULTS:

One of three cell lines tested was identified to be adhesive to endothelial cells and express VCAM-1. Adherence ability of the cells was dramatically decreased by neutralization of surface VCAM-1. VCAM-1 was co-localized with Caveolin-1 and siRNA-mediated knockdown of Caveolin-1 expression significantly blocked the VCAM-1-dependent cell adhesion.

CONCLUSIONS:

Our data imply important roles for VCAM-1 and Caveolin- 1 in the regulation of metastatic potential of gastric tumor cells.

• Authors: Jaeyoung Shin, Jongmin Kim, Byungkyu Ryu, Sung-Gil Chi, Heonyong Park
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 17 Issue 5-6 Pg. 211-20 ( 2006) ISSN: 1015-8987 [Print] Germany
• PMID: 16790997 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Caveolin 1
• Enzyme Inhibitors
• Imidazoles
• Pyridines
• Vascular Cell Adhesion Molecule-1
• p38 Mitogen-Activated Protein Kinases
• 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole

Topics

• Animals
• Cattle
• Caveolae (metabolism)
• Caveolin 1 (drug effects, genetics, metabolism)
• Cell Adhesion (drug effects, physiology)
• Endothelial Cells (cytology, metabolism)
• Enzyme Inhibitors (pharmacology)
• Humans
• Imidazoles
• Pyridines
• Stomach Neoplasms (metabolism, pathology)
• Tumor Cells, Cultured
• Vascular Cell Adhesion Molecule-1 (drug effects, genetics, metabolism)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)