Dual roles of sialyl Lewis X oligosaccharides in tumor metastasis and rejection by natural killer cells

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 we re stably transfected with alg-fucosyltransferase III to express sialyl Lew is 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 n odules, Surprisingly, B16-FTIII.H cells expressing the highest amount of si alyl 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 contras t, B16-FIII.H cells formed more tumors in beige mice and NK cell-depleted C 57BL/6 mice than did B16-FTIII.M cells. B16FTIII.H cells bound to E-selecti n 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 facilitat ed by attachment to endothelial cells.