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Dual roles of sialyl Lewis X oligosaccharides in tumor metastasis and rejection by natural killer cells.

Abstract
Aberrant expression of cell surface carbohydrates such as sialyl Lewis X is associated with tumor formation and metastasis. In order to determine the roles of sialyl Lewis X in tumor metastasis, mouse melanoma B16-F1 cells were stably transfected with alpha1, 3-fucosyltransferase III to express sialyl Lewis X structures. The transfected B16-F1 cells, B16-FTIII, were separated by cell sorting into three different groups based on the expression levels of sialyl Lewis X. When these transfected cells were injected into tail veins of C57BL/6 mice, B16-FTIII.M cells expressing moderate amounts of sialyl Lewis X in poly-N-acetyllactosamines produced large numbers of lung tumor nodules. Surprisingly, B16-FTIII.H cells expressing the highest amount of sialyl Lewis X in shorter N-glycans died in lung blood vessels, producing as few lung nodules as B16-FTIII.N cells which lack sialyl Lewis X. In contrast, B16-FIII.H cells formed more tumors in beige mice and NK cell-depleted C57BL/6 mice than did B16-FTIII.M cells. B16-FTIII.H cells bound to E-selectin better than did B16-FTIII.M cells, but both cells grew at the same rate. These results indicate that excessive expression of sialyl Lewis X in tumor cells leads to rejection by NK cells rather than tumor formation facilitated by attachment to endothelial cells.
AuthorsC Ohyama, S Tsuboi, M Fukuda
JournalThe EMBO journal (EMBO J) Vol. 18 Issue 6 Pg. 1516-25 (Mar 15 1999) ISSN: 0261-4189 [Print] England
PMID10075923 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • E-Selectin
  • Lewis X Antigen
  • Oligosaccharides
  • Recombinant Proteins
  • Sialyl Lewis X Antigen
  • Fucosyltransferases
  • galactoside 3-fucosyltransferase
Topics
  • Animals
  • Cell Division
  • Cytotoxicity, Immunologic
  • E-Selectin (physiology)
  • Flow Cytometry
  • Fucosyltransferases (genetics, metabolism)
  • Graft Rejection (immunology, pathology)
  • Killer Cells, Natural (immunology)
  • Lewis X Antigen (immunology)
  • Lung Neoplasms (immunology, pathology, secondary)
  • Melanoma, Experimental (immunology, pathology)
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Metastasis
  • Neoplasm Transplantation (immunology, pathology)
  • Oligosaccharides (chemistry, immunology)
  • Recombinant Proteins (metabolism)
  • Sialyl Lewis X Antigen
  • Transfection
  • Tumor Cells, Cultured

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