Hyposialylation of high-molecular-weight membrane glycoproteins parallels the loss of metastatic potential in wheat-germ agglutinin-resistant Friend leukemia cells.
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 (125I)-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 (125I)-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 (125I)-LPHA, (125I)-ConA and (125I)-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.
Benedetto
A
A
Centre of Virology, Ospedale S. Camillo, Rome, Italy.
Elia
G
G
Sala
A
A
Belardelli
F
F
D000818:Animals; D005260:Female; D005622:Friend murine leukemia virus; D007942:Leukemia, Experimental / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D008970:Molecular Weight; D009362:Neoplasm Metastasis; D011975:Receptors, Mitogen / Q000378:metabolism; D014909:Wheat Germ Agglutinins
D008562:Membrane Glycoproteins; D011975:Receptors, Mitogen; D014909:Wheat Germ Agglutinins; C027503:wheat germ agglutinin receptor