Cyclooxygenase-2 activity altered the cell-surface carbohydrate antigens on colon cancer cells and enhanced liver metastasis.

Abstract

Cyclooxygenase-2 (COX-2) was recently reported (M. Tsujii and R. N. DuBois, Cell, 83: 493-501, 1995) to affect the metastatic potential of cells. Previous studies (M. Fukuda, Cancer Res., 56: 2237-2244, 1996) indicated that sialyl Lewis antigen expression is correlated with hematogenous metastasis of colon cancer. In the present study, we investigated the interaction between COX-2 activity, expression of sialyl Lewis antigens, in vitro cancer cell adhesion to endothelial cells, and in vivo metastatic potential. Effects of COX-2 activity and prostaglandin E(2) on cell adhesion, expression of sialyl Lewis antigens, and glycosyltransferase genes were determined in Caco-2-m (COX-2 low level), Caco-2-COX-2 (programmed to overexpress COX-2), and HT-29 (COX-2 high level) cells. Metastatic spread of these cells to the liver was also investigated. Caco-2-COX-2 cells had increased SPan-1 levels and increased adherence to endothelial cells via SPan-1 compared with Caco-2-m cells. HT-29 cells expressed sialyl Lewis a and adhered to endothelial cells via sialyl Lewis a. Treatment with a COX-2 inhibitor, celecoxib, decreased SPan-1 and sialyl Lewis a expression and adherence to endothelial cells. beta 3Gal-T5 and ST3Gal III and IV expression was inhibited by celecoxib and was enhanced by prostaglandin E(2) treatment. Caco-2-COX-2 and HT-29 cells metastasized to the liver, whereas Caco-2-m cells did not. Pretreatment with celecoxib reduced the metastatic potential as well as anti-sialyl Lewis antibodies. Our results indicate a direct link between COX-2 and enhanced adhesion of carcinoma cells to endothelial cells, and enhanced liver metastatic potential via accelerated production of sialyl Lewis antigens. COX-2 inhibitors may suppress metastasis.

• Authors: Yoshimi Kakiuchi, Shingo Tsuji, Masahiko Tsujii, Hiroaki Murata, Naoki Kawai, Masakazu Yasumaru, Arata Kimura, Masato Komori, Takanobu Irie, Eiji Miyoshi, Yutaka Sasaki, Norio Hayashi, Sunao Kawano, Masatsugu Hori
• Journal: Cancer research (Cancer Res) Vol. 62 Issue 5 Pg. 1567-72 (Mar 01 2002) ISSN: 0008-5472 [Print] United States
• PMID: 11888937 (Publication Type: Journal Article)

Chemical References

• Isoenzymes
• Membrane Proteins
• Oligosaccharides
• Sialyl Lewis X Antigen
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases
• Glycosyltransferases
• Dinoprostone

Topics

• Animals
• Caco-2 Cells
• Cell Adhesion
• Colonic Neoplasms (enzymology, immunology, pathology)
• Cyclooxygenase 2
• Dinoprostone (biosynthesis, pharmacology)
• Endothelium, Vascular (cytology)
• Glycosyltransferases (physiology)
• HT29 Cells
• Humans
• Isoenzymes (physiology)
• Liver Neoplasms (secondary)
• Male
• Membrane Proteins
• Mice
• Mice, Inbred BALB C
• Oligosaccharides (analysis)
• Prostaglandin-Endoperoxide Synthases (physiology)
• Sialyl Lewis X Antigen