title: Binding sites for Lewis antigens are expressed by human colon cancer cells and negatively affect their migration.
abstract: In colon cancer, endothelial cell selectins can promote tumor cell attachment via interactions with sialylated Lewis antigens present at the surface of tumor cells, thereby facilitating tumor cell arrest and transmigration into the extravascular space. However, it is not known whether Lewis antigens interact with colon tumor cells and modify their migration. Our aim was to detect the presence of binding sites on human tumor cells for Lewis(a/x) antigens and their sialylated derivatives in vitro and in vivo and to analyze their influence on migration of colon cancer cells. The immunocytochemical and histochemical levels of expression of the four Lewis antigens were quantitatively determined in four human colon cancer cell lines and in in vivo nude mice xenografts. The levels of expression of specific binding sites for these sugar epitopes were determined by synthetic neoglycoconjugates. The influence of binding of these carbohydrate ligands on cancer cell migration was quantitatively evaluated by computer-assisted phase-contrast videomicroscopy performed on Matrigel culture supports either left uncoated or coated with neoglycoconjugate presenting synthetic Lewis(a), sialyl Lewis(a), Lewis(x), or sialyl Lewis(x) antigens. The influence of the calcium concentration in the culture medium on the Lewis antigen-mediated effects was checked. Human colon cancer cells expressed significant amounts of specific binding sites detected by the synthetic probes in addition to the oligosaccharide epitopes. The expression levels differed considerably between the four cell lines and between in vitro and in vivo specimens. Cell migration analysis revealed that the four Lewis antigens markedly decreased the levels of migration of the HCT-15 and LoVo cancer cells. This effect depends on the calcium concentration in the culture medium. Binding sites for Lewis epitopes are present on colon cancer cells. The functional relevance of these sites is indicated by the negative influence on cell migration of a matrix containing the oligosaccharides as ligand parts.
authors.affiliation: Department of Gastroenterology, Erasmus University Hospital, Faculty of Medicine, Université Libre de Bruxelles, Jules Bordet Institute, Brussels, Belgium.
authors.forename: Axel
authors.initials: A
authors.lastname: Hittelet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Camby
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nagy
authors.forename: Hugues
authors.initials: H
authors.lastname: Legendre
authors.forename: Yves
authors.initials: Y
authors.lastname: Bronckart
authors.forename: Christine
authors.initials: C
authors.lastname: Decaestecker
authors.forename: Herbert
authors.initials: H
authors.lastname: Kaltner
authors.forename: Nikolay E
authors.initials: NE
authors.lastname: Nifant'ev
authors.forename: Nicolai V
authors.initials: NV
authors.lastname: Bovin
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Pector
authors.forename: Isabelle
authors.initials: I
authors.lastname: Salmon
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.forename: Paul
authors.initials: P
authors.lastname: Yeaton
mesh_terms: D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D003110:Colonic Neoplasms / Q000503:physiopathology*; D005260:Female; D006001:Glycoconjugates / Q000378:metabolism; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D006001:Glycoconjugates; D007983:Lewis Blood Group Antigens