Natural killer cells attack tumor cells expressing high levels of sialyl Lewis x oligosaccharides.
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.
Ohyama
Chikara
C
Department of Urology, Akita University School of Medicine, Akita 010-8543, Japan.
Kanto
Satoru
S
Kato
Kazunori
K
Nakano
Osamu
O
Arai
Yoichi
Y
Kato
Tetsuro
T
Chen
Shihao
S
Fukuda
Michiko N
MN
Fukuda
Minoru
M
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D051920:NK Cell Lectin-Like Receptor Subfamily D; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009844:Oligosaccharides / Q000235:genetics / Q000276:immunology*; D000080506:Sialyl Lewis X Antigen; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C497869:KLRD1 protein, human; C497870:Klrd1 protein, mouse; D037181:Lectins, C-Type; D051920:NK Cell Lectin-Like Receptor Subfamily D; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D005647:Fucosyltransferases; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase