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

Abstract
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.
AuthorsM Aubert, L Panicot-Dubois, C Crotte, V Sbarra, D Lombardo, M O Sadoulet, E Mas
JournalInternational journal of cancer (Int J Cancer) Vol. 88 Issue 4 Pg. 558-65 (Nov 15 2000) ISSN: 0020-7136 [Print] United States
PMID11058871 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2000 Wiley-Liss, Inc.
Chemical References
  • E-Selectin
  • Oligosaccharides
  • RNA, Antisense
  • RNA, Messenger
  • Sialyl Lewis X Antigen
  • Fucosyltransferases
  • 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase
Topics
  • Animals
  • CHO Cells
  • Cricetinae
  • E-Selectin (genetics, physiology)
  • Female
  • Fucosyltransferases (genetics, metabolism)
  • Humans
  • Mice
  • Mice, Nude
  • Oligosaccharides (analysis)
  • Pancreatic Neoplasms (enzymology, genetics, pathology)
  • Peritoneal Neoplasms (genetics, pathology, prevention & control, secondary)
  • RNA, Antisense (genetics)
  • RNA, Messenger (genetics)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialyl Lewis X Antigen
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

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