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 t ransfer to galactose of the N-acetyl(iso)lactosamine chain is decreased in human metastatic pancreatic cancer cells. alpha(2,3) Sialyltransferases cat alyze 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 determinan ts 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) fuc osyltransferase expression can favor the alpha(2,3) sialyltransferase activ ity to form metastatic sialyl-Lewis antigens. Restoration of alpha(1,2) fuc osyltransferase activity in the human pancreatic cancer cell line BxPC-3 wa s obtained by selecting stable transfectants expressing FUT1. Overexpressio n of FUT1 in BxPC-3 cells resulted in a substantial reduction of sialyl-Lew is antigen expression that correlated with an increase of expression of Lew is y and H-type antigens on cell surface. The modified oligosaccharide stru ctures were preferentially restricted to three major glycoproteins, which c ould in part be related to mucin-type glycoproteins. The reduction of sialy l-Lewis antigen expression was associated with an inhibition of adhesive pr operties 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) fucosyltransferas e 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.