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Recognition of Asparagine-linked Oligosaccharides on Murine Tumor Cells by Natural Killer Cells¹

Cancer Research Laboratories, Department of Pathology, Queen's University, Kingston, Ontario, Canada K7L 3N6

MDW4, a wheat germ agglutinin resistant mutant of the murine tumor line MDAY-D2, expresses abnormal asparagine-linked oligosaccharides, is less metastatic when injected intravenously, and is hypersensitive to natural killer (NK) lysis in vitro. To determine whether these phenotypes may be related, variants of the YAC-1 lymphoma and a YAC-1 x MDAY-D2 hybrid line were compared for sensitivity to four different lectins and to NK cell lysis in vitro. A relationship between sensitivity to concanavalin A (Con A) and NK cell lysis in vitro was observed. Although no single plasma membrane glycoprotein separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and stained with ¹²⁵I-labeled Con A correlated with NK and Con A sensitivities of the cell lines, a relationship between these phenotypes and the collective ¹²⁵I-Con A staining intensity on the gels was apparent. In a more direct test of carbohydrate recognition by NK cells, specific glycopeptide structures isolated from tumor cells and added to the NK cell assay in µM quantities were found to inhibit tumor cell lysis. Thus, a subset of asparagine-linked oligosaccharides, including high mannose and some incomplete complex structures on a number of cell surface glycoproteins, appears to be recognized as part of the target structures for NK cell lysis. The administration of polyinosinic:polycytidylic acid stimulated splenic NK activity in vivo but had no effect on the growth of the NK-resistant MDAY-D2 cells. However, the low tumorigenicity of MDW4 cells injected intravenously was reduced further by pretreating the mice with polyinosinic:polycytidylic acid, which indicated a role for NK cells in the elimination of circulating tumor cells expressing high mannose and/or incomplete complex asparagine-linked oligosaccharides.

¹ This work was supported by grants from the National Cancer Institute of Canada and the Medical Research Council of Canada (J. W. D.).

² To whom requests for reprints should be addressed, at Room 880, Division of Cancer Research, Mount Sinai Research Institute, 600 University Avenue, Toronto, Ontario, Canada, M5G 1X5.

³ Postdoctoral Fellow of the National Cancer Institute of Canada.

Received 3/26/85. Revised 8/23/85. Accepted 8/28/85.