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.
Aubert
M
M
Inserm Unité 260. Unité de Recherche de Physiopathologie des Régulations Hormono-Nutritionnelles, Marseille, France.
Panicot-Dubois
L
L
Crotte
C
C
Sbarra
V
V
Lombardo
D
D
Sadoulet
M O
MO
Mas
E
E
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D019040:E-Selectin / Q000235:genetics / Q000502:physiology; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009844:Oligosaccharides / Q000032:analysis; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control / Q000556:secondary*; D016372:RNA, Antisense / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000080506:Sialyl Lewis X Antigen; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D019040:E-Selectin; D009844:Oligosaccharides; D016372:RNA, Antisense; D012333:RNA, Messenger; D000080506:Sialyl Lewis X Antigen; D005647:Fucosyltransferases; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase