Binding sites for Lewis antigens are expressed by human colon cancer cells and negatively affect their migration.
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.
Hittelet
Axel
A
Department of Gastroenterology, Erasmus University Hospital, Faculty of Medicine, Université Libre de Bruxelles, Jules Bordet Institute, Brussels, Belgium.
Camby
Isabelle
I
Nagy
Nathalie
N
Legendre
Hugues
H
Bronckart
Yves
Y
Decaestecker
Christine
C
Kaltner
Herbert
H
Nifant'ev
Nikolay E
NE
Bovin
Nicolai V
NV
Pector
Jean-Claude
JC
Salmon
Isabelle
I
Gabius
Hans-Joachim
HJ
Kiss
Robert
R
Yeaton
Paul
P
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
D006001:Glycoconjugates; D007983:Lewis Blood Group Antigens