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Dual roles of sialyl Lewis X oligosaccharides in tumor metastasis and rejection by natural killer cells
Author(s) -
Ohyama Chikara,
Tsuboi Shigeru,
Fukuda Minoru
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.6.1516
Subject(s) - biology , metastasis , sialyl lewis x , dual (grammatical number) , natural killer cell , cancer research , tumor cells , immunology , microbiology and biotechnology , cancer , biochemistry , genetics , cytotoxicity , in vitro , inflammation , art , literature , selectin
Aberrant expression of cell surface carbohydrates such as sialyl Lewis X is associated with tumor formation and metastasis. In order to determine the roles of sialyl Lewis X in tumor metastasis, mouse melanoma B16‐F1 cells were stably transfected with α1,3‐fucosyltransferase III to express sialyl Lewis X structures. The transfected B16‐F1 cells, B16‐FTIII, were separated by cell sorting into three different groups based on the expression levels of sialyl Lewis X. When these transfected cells were injected into tail veins of C57BL/6 mice, B16‐FTIII·M cells expressing moderate amounts of sialyl Lewis X in poly‐ N ‐acetyllactosamines produced large numbers of lung tumor nodules. Surprisingly, B16‐FTIII·H cells expressing the highest amount of sialyl Lewis X in shorter N ‐glycans died in lung blood vessels, producing as few lung nodules as B16‐FTIII·N cells which lack sialyl Lewis X. In contrast, B16‐FIII·H cells formed more tumors in beige mice and NK cell‐depleted C57BL/6 mice than did B16‐FTIII·M cells. B16‐FTIII·H cells bound to E‐selectin better than did B16‐FTIII·M cells, but both cells grew at the same rate. These results indicate that excessive expression of sialyl Lewis X in tumor cells leads to rejection by NK cells rather than tumor formation facilitated by attachment to endothelial cells.