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Natural killer cells attack tumor cells expressing high levels of sialyl Lewis x oligosaccharides.

Abstract
Epithelial carcinoma and leukemia cells express sialyl Lewis x oligosaccharides as tumor-associated carbohydrate antigens. To determine the role of sialyl Lewis x oligosaccharides in tumor dissemination, human melanoma MeWo cells, which do not express sialyl Lewis x, were transfected with alpha1,3-fucosyltransferase III (FTIII), and cell lines expressing different amounts of sialyl Lewis x were isolated. When these cells were injected into the tail vein of nude mice, cells expressing moderate amounts of sialyl Lewis x (MeWo-FTIII.M) produced a significantly greater number of lung tumor foci than did parental MeWo cells. In contrast, cells expressing large amounts of sialyl Lewis x (MeWo-FTIII.H) produced few lung tumor foci in nude mice but were highly tumorigenic in beige mice, which have defective natural killer (NK) cells. In vitro assays demonstrated that MeWo-FTIII.H cells are much more sensitive to NK cell-mediated cytotoxicity than are MeWo-FTIII.M cells or parental MeWo cells and the susceptibility of MeWo-FTIII.H cells to NK cell-mediated cytolysis can be inhibited by preincubating MeWo-FTIII.H cells with anti-sialyl Lewis x antibody. Moreover, we discovered that NK cell-mediated cytolysis of MeWo-FTIII.H cells can be inhibited by the addition of an antibody against the NK cell receptor CD94 or sialyl Lewis x oligosaccharides. These results, combined with structural analysis of MeWo-FTIII.H cell carbohydrates, indicate that moderate amounts of sialyl Lewis x lead to tumor metastasis, whereas expression of high levels of sialyl Lewis x leads to an NK cell attack on tumor cells, demonstrating that expression of different amounts of sialyl Lewis x results in entirely different biological consequences.
AuthorsChikara Ohyama, Satoru Kanto, Kazunori Kato, Osamu Nakano, Yoichi Arai, Tetsuro Kato, Shihao Chen, Michiko N Fukuda, Minoru Fukuda
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 99 Issue 21 Pg. 13789-94 (Oct 15 2002) ISSN: 0027-8424 [Print] United States
PMID12370411 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigens, CD
  • KLRD1 protein, human
  • Klrd1 protein, mouse
  • Lectins, C-Type
  • NK Cell Lectin-Like Receptor Subfamily D
  • Oligosaccharides
  • Sialyl Lewis X Antigen
  • Fucosyltransferases
  • 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase
Topics
  • Animals
  • Antigens, CD (immunology)
  • Cytotoxicity, Immunologic
  • Female
  • Fucosyltransferases (genetics)
  • Gene Expression
  • Humans
  • Killer Cells, Natural (immunology)
  • Lectins, C-Type (immunology)
  • Lung Neoplasms (genetics, immunology, pathology, secondary)
  • Mice
  • Mice, Nude
  • Mice, SCID
  • NK Cell Lectin-Like Receptor Subfamily D
  • Neoplasms, Experimental (genetics, immunology, pathology)
  • Oligosaccharides (genetics, immunology)
  • Sialyl Lewis X Antigen
  • Transfection
  • Tumor Cells, Cultured

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