Natural Killer Cells Attack Tumor Cells Expressing High Levels of Sialyl Lewis x Oligosaccharides

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 99; no. 21; pp. 13789 - 13794
• Main Authors: Ohyama, Chikara, Kanto, Satoru, Kato, Kazunori, Nakano, Osamu, Arai, Yoichi, Kato, Tetsuro, Chen, Shihao, Fukuda, Michiko N., Fukuda, Minoru
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 15.10.2002; National Acad Sciences; The National Academy of Sciences
• Subjects: Animals; Antibodies; Antigens, CD - immunology; Biological Sciences; Cell lines; Cytolysis; Cytotoxicity; Cytotoxicity, Immunologic; Female; Fucosyltransferases - genetics; Gene Expression; Glycopeptides; Humans; Immunology; Killer Cells, Natural - immunology; Lectins, C-Type - immunology; Leukemia; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Lung Neoplasms - secondary; Lungs; Medical research; Mice; Mice, Nude; Mice, SCID; Natural killer cells; Neoplasms, Experimental - genetics; Neoplasms, Experimental - immunology; Neoplasms, Experimental - pathology; NK Cell Lectin-Like Receptor Subfamily D; Oligosaccharides; Oligosaccharides - genetics; Oligosaccharides - immunology; Receptors; Transfection; Tumor Cells, Cultured; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.212456599

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 α1,3-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.