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.
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Authors | Chikara Ohyama, Satoru Kanto, Kazunori Kato, Osamu Nakano, Yoichi Arai, Tetsuro Kato, Shihao Chen, Michiko N Fukuda, Minoru Fukuda |
Journal | Proceedings 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 |
PMID | 12370411
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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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
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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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