title: 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.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan. kakiuchi@medone.osaka-u.ac.jp
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Kakiuchi
authors.forename: Shingo
authors.initials: S
authors.lastname: Tsuji
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tsujii
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Murata
authors.forename: Naoki
authors.initials: N
authors.lastname: Kawai
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yasumaru
authors.forename: Arata
authors.initials: A
authors.lastname: Kimura
authors.forename: Masato
authors.initials: M
authors.lastname: Komori
authors.forename: Takanobu
authors.initials: T
authors.lastname: Irie
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
authors.forename: Sunao
authors.initials: S
authors.lastname: Kawano
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002448:Cell Adhesion; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology; D016695:Glycosyltransferases / Q000502:physiology; D019073:HT29 Cells; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009844:Oligosaccharides / Q000032:analysis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D000080506:Sialyl Lewis X Antigen
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D016695:Glycosyltransferases; D015232:Dinoprostone