Peritoneal colonization by human pancreatic cancer cells is inhibited by antisense FUT3 sequence

Several alpha(1,3/1,4) fucosyltransferases expressed in human pancreatic Cancer cells can participate in the biosynthesis of cell surface sialyl-Lewis a and sialyl-Lewis x antigens that contribute to hematogenous metastatis. Previously, we observed a significant increase of the alpha(1,4) fucosyltransferase activity in tumoral pancreatic cell lines, suggesting that FUT3 could be involved in the sialyl-Lewis antigen expression. Therefore, we invalidated the expression of FUT3 by expressing FUT3 antisense sequence in the human pancreatic tumor BxPC-3 cell line, which expresses the alpha(1,4) fucosyltransferase activity and harbors the cell surface sialyl-Lewis antigens. The decrease of FUT3 transcript after transfection of antisense cDNA of FUT3 in these cells results in a substantial reduction of sialyl-Lewis antigen expression on cell surface. This decreased antigen expression was associated with an inhibition of adhesive properties to E-Selectin and a decrease of metastatic power of FUT3 antisense-transfected BxPC-3 cells as tested in nude mice. Our study provides evidence that the expression level of FUT3 may regulate the expression of sialyl-Lewis a and sialyl-Lewis x surface antigens and consequently could play an important role in metastatic properties of human pancreatic Cancer cells.