Different metastatic phenotypes in two genetic classes of wheat germ agglutinin-resistant tumor cell mutants.

Spontaneous wheat germ agglutinin (WGA)-resistant mutants of the highly metastatic tumor line MDAY-D2 have been grouped into two classes by (a) genetic complimentation in somatic cell hybrids, (b) lectin binding to plasma membrane glycoproteins, and (c) metastatic phenotypes. Class 1 mutants were recessive in somatic cell hybrids between mutant and wild type cells; they were poorly metastatic in an organ colonization assay and nonmetastatic in the spontaneous metastasis assay. The class 1 mutants had prematurely truncated asparagine-linked oligosaccharides terminating in N-acetylglucosamine, rather than the sialylated N-acetyllactosamine found in wild type cells. The class 2 mutation was dominant in somatic cell hybrids between mutant and wild type cells. The cell lines retained the highly metastatic phenotype in both organ colonization and spontaneous metastasis assays. The plasma membrane glycoproteins of the class 2 mutants were similar to those of MDAY-D2 cells including the presence of sialylated polylactosamine-containing antennae in the asparagine-linked oligosaccharide. However, the cells synthesized N-glycolylneuraminic acid rather than the N-acetylneuraminic acid, a form of sialic acid that does not bind WGA. Previous studies by other investigators have shown that lectin-resistant mutants selected in WGA were often less metastatic than their respective wild type cell. Our results demonstrate that the loss of metastatic potential in WGA-resistant mutants of MDAY-D2 depends on the phenotypic class of the isolates and their characteristic changes in glycoconjugate structure.