Restoration of alpha(1,2) fucosyltransferase activity decreases adhesive and metastatic properties of human pancreatic cancer cells.
The expression of alpha(1,2) fucosyltransferases that catalyze the fucose transfer to galactose of the N-acetyl(iso)lactosamine chain is decreased in human metastatic pancreatic cancer cells. alpha(2,3) Sialyltransferases catalyze the transfer of sialic acid to the same substrate to form, with alpha(1,3/1,4) fucosyltransferases, sialyl-Lewis a and sialyl-Lewis x determinants on cell surface that are involved in pancreatic metastatic invasion. The aim of this study was to determine whether this decrease of alpha(1,2) fucosyltransferase expression can favor the alpha(2,3) sialyltransferase activity to form metastatic sialyl-Lewis antigens. Restoration of alpha(1,2) fucosyltransferase activity in the human pancreatic cancer cell line BxPC-3 was obtained by selecting stable transfectants expressing FUT1. Overexpression of FUTI in BxPC-3 cells resulted in a substantial reduction of sialyl-Lewis antigen expression that correlated with an increase of expression of Lewis y and H-type antigens on cell surface. The modified oligosaccharide structures were preferentially restricted to three major glycoproteins, which could in part be related to mucin-type glycoproteins. The reduction of sialyl-Lewis antigen expression was associated with an inhibition of adhesive properties to E-selectin and a decrease of gastrointestinal metastatic power of BxPC-3 cells after xenograft transplantation into nude mice. This study provides evidence that the expression level of alpha(1,2) fucosyltransferase may regulate the expression of sialyl-Lewis a and sialyl-Lewis x antigens and consequently could play an important role in metastatic properties of human pancreatic cancer cells.
Aubert
M
M
Institut National de la Santé et de la Recherche Médicale Unité 260, Faculté de Médecine, Marseille, France.
Panicot
L
L
Crotte
C
C
Gibier
P
P
Lombardo
D
D
Sadoulet
M O
MO
Mas
E
E
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D004789:Enzyme Activation; D005647:Fucosyltransferases / Q000096:biosynthesis* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase