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

• Published in: International journal of cancer Vol. 88; no. 4; pp. 558 - 565
• Main Authors: Aubert, Muriel, Panicot‐Dubois, Laurence, Crotte, Christian, Sbarra, Véronique, Lombardo, Dominique, Sadoulet, Marie‐Odile, Mas, Eric
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 15.11.2000; Wiley-Liss
• Subjects: Animal tumors. Experimental tumors; Animals; Biological and medical sciences; CHO Cells; Cricetinae; E-Selectin - genetics; E-Selectin - physiology; Experimental tumors, general aspects; Female; Fucosyltransferases - genetics; Fucosyltransferases - metabolism; FUT3 gene; Humans; Medical sciences; Mice; Mice, Nude; Oligosaccharides - analysis; Pancreatic Neoplasms - enzymology; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Peritoneal Neoplasms - genetics; Peritoneal Neoplasms - pathology; Peritoneal Neoplasms - prevention & control; Peritoneal Neoplasms - secondary; Reverse Transcriptase Polymerase Chain Reaction; RNA, Antisense - genetics; RNA, Messenger - genetics; sialyl Lewis a antigen; sialyl Lewis x antigen; Transcription, Genetic; Tumor Cells, Cultured; Tumors; Xenograft Model Antitumor Assays; Human; Animal model; Carbohydrate antigen; Carcinoma; Tumor associated antigen; Enzyme; Rodentia; Tumoral marker; Malignant tumor; Metastasis; Vertebrata; Mammalia; Mouse; Sialyl Lewis x antigen; Abdominal disease; Animal; Established cell line; Digestive diseases; Pancreas; Antigen CA 19 9; Pancreatic disease; Peritoneum
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/1097-0215(20001115)88:4<558::AID-IJC7>3.0.CO;2-B

Several α(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 α(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 α(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. Int. J. Cancer 88:558–565, 2000. © 2000 Wiley‐Liss, Inc.