Co-reversion of a lectin-resistant mutation and non-metastatic phenotype in murine tumor cells.

Three independent isolates, one obtained spontaneously and the others obtained after in vitro mutagenesis, of a WGA-resistant mutation were compared to the highly metastatic parental murine cell line MDAY-D2 for alterations in plasma membrane glycoproteins and changes in metastatic behavior. The mutants were non-metastatic from an s.c. site of injection and poor organ-colonizers when administered i.v. Each of the mutant lines had the same lesion in N-linked oligosaccharide structure, which rendered the cells hypersensitive to the N-acetylglucosamine-binding lectin BSII in vitro. The phenotypic similarities between the 3 WGA-resistant isolates indicated that the mutation was directly related to the attenuated malignant phenotype. Direct confirmation was obtained by the isolation of a BSII-resistant clone of the mutant cells that co-reverted for lectin-sensitivity, lectin binding glycoproteins and malignant aggressiveness. The results indicate a direct relationship between malignant behavior and cell-surface oligosaccharide structure.