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| The EMBO Journal
(1999) 18, 1516–1525, doi:10.1093/emboj/18.6.1516 |
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| Dual roles of sialyl Lewis X oligosaccharides in tumor metastasis and rejection by natural killer cells |
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| Chikara Ohyama, Shigeru Tsuboi and Minoru Fukuda |
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Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA To whom correspondence should be addressed Minoru Fukuda, minoru@burnham-inst.org Received 10 December 1998; Revised 26 January 1999; Accepted 26 January 1999. |
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| Abstract |
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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  1,3-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-FTIIIH 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-FTIIIN cells which lack sialyl Lewis X. In contrast, B16-FIIIH cells formed more tumors in beige mice and NK cell-depleted C57BL/6 mice than did B16-FTIIIM cells. B16-FTIIIH cells bound to E-selectin better than did B16-FTIIIM 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. |
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| Keywords: NK cells, selectin, sialyl Lewis X, tumor cell rejection, tumor metastasis |
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