Spontaneous
wheat germ agglutinin (WGA)-resistant mutants of the MeWo human
malignant melanoma line were isolated after sequential selection in increasingly toxic concentrations of WGA, without prior mutagenesis. They were isolated in an attempt to obtain "membrane glycosylation mutants" having significantly altered metastatic properties when grown in nude mice, and to characterize the biochemical (
oligosaccharide) changes associated with altered metastatic behavior. The lines were assessed for their sensitivity to other
lectins,
membrane glycoprotein profiles, ploidy levels, and their ability to produce "artificial"
metastases in nude mice after i.v. inoculation. One mutant, called 70-W, manifested a 3- to 4-fold resistance to WGA compared with wild-type cells. When inoculated into NIH Swiss nude mice, 70-W cells not only produced extensive lung colony formation but also showed an extraordinary ability to disseminate widely and extensively in a clinical fashion to many extrapulmonary sites such as the subcutis, mesentery, muscle, and brain. Moreover the majority of these
metastases were deeply pigmented facilitating visual identification of very small visceral
metastases. A second mutant called 3S5 was isolated and found to be highly resistant to WGA (greater than 20-fold resistance). This line was virtually devoid of metastatic ability and was found by biochemical analysis to be phenotypically similar to the class I WGA resistant non-metastatic mutants previously isolated from the highly metastatic murine
tumor MDAY-D2 which are known to be deficient in
sialic acid and
galactose. The similarity between these and earlier results using
lectin resistant mutant rodent cell lines strongly suggests that sialylated
glycoconjugates contribute to the
metastasis of both animal and human
tumors of different tissue origin. These new spontaneously derived WGA resistant MeWo mutants should be valuable new tools for the study of human
tumor progression in vivo and factors involved in
metastasis, especially the contribution of
oligosaccharide moieties of cell surface
glycoconjugates.