Increased fucosylation of glycolipids in a human leukaemia cell line (K562-Clone I) with decreased sensitivity to NK-mediated lysis.
A subpopulation of human lymphoid cells called natural killers is able to lyse certain normal and neoplastic targets in an in vitro cytotoxicity assay. The molecules which enable them to recognize sensitive cells, or permit tumour cells to escape remain unknown. In the studies described here we have compared some of the plasma membrane characteristics of a NK-sensitive human leukaemia cell line (K562) with those of a partially resistant subclone derived from it (K562-Clone I). Gel electrophoresis of cell-surface proteins radiolabelled by lactoperoxidase-catalysed iodination, periodate-borohydride tritiation, or biosynthetically by incubation with [3H]fucose did not reveal any reproducible differences between the sensitive and resistant lines. However, analysis of glycolipids showed that Clone I incorporated significantly more fucose than did the parental line, and that it synthesized a minor population of complex structures not found in the original K562. A subclone of Clone I (Clone I-Con Ar1), made resistant to the toxic effects of concanavalin A, became sensitive once again to NK, and showed the parental glycolipid profile. These results suggest that the Clone I line, selected for resistance to NK, may have altered one or more of its intermediate oligosaccharides or pathways of fucose incorporation into glycolipid, and points to one process by which a tumor cell might modulate its surface to escape recognition by natural killers.
D000951:Antigens, Neoplasm / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004591:Electrophoresis, Polyacrylamide Gel; D005643:Fucose / Q000378:metabolism*; D006017:Glycolipids / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D007938:Leukemia / Q000276:immunology* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000032:analysis
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D006017:Glycolipids; D009363:Neoplasm Proteins; D005643:Fucose