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

Chikara Ohyama, Satoru Kanto, Kazunori Kato, Osamu Nakano, Yoichi Arai, Tetsuro Kato, Shihao Chen, Michiko N. Fukuda, Minoru Fukuda

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48 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)13789-13794
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number21
DOIs
Publication statusPublished - 2002 Oct 15

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