Hyposialylation of high‐molecular‐weight membrane glycoproteins parallels the loss of metastatic potential in wheat‐germ agglutinin‐resistant friend leukemia cells

Abstract

From the highly metastatic in vivo‐passaged Friend leukemia cells (FLC), WGA‐resistant (WR) tumor cell variants were selected. These WR FLC had lost their capacity to metastasize when injected i.v. or s.c. into DBA/2 mice. We have characterized the plasma membrane glycoproteins of the different FLC types by: (i) metabolic labelling with (³H)‐galactose; (ii) surface labelling with galactose oxidase‐borohydride; (iii) direct binding of (¹²⁵l)‐lectins on glycoproteins separated by SDS‐PAGE. The ensemble of these approaches showed that the 100‐ to 200‐kDa glycoproteins of in vivo‐passaged FLC and WR FLC exhibited a very similar distribution of the terminal galactose in their oligosaccharide moieties. In contrast, the expression of terminal sialic acid was reduced in WR FLC with respect to in vivo‐passaged counterparts as appreciated by: (i) binding experiments with (¹²⁵l)‐WGA; (ii) cathodic shift of the 100‐ to 200‐kDa glycoproteins in 2‐dimensional electrophoresis studies, and (iii) thiobarbituric acid assay after FLC treatment with neuraminidase. Moreover, binding experiments with (¹²⁵l)‐LPHA, (¹²⁵l)‐ConA and (¹²⁵l)‐WGA (after Smith degradation) indicated that, in the 100‐to 200‐kDa region, virtually identical asparagine‐linked tri‐ or tetra‐antennary complex‐type oligosaccharides were expressed in both cell types. We conclude that the sialylation of high‐molecular‐weight surface glycoproteins (particularly in the 150‐kDa region) is strongly associated with the metastatic potential of FLC, especially to the liver.