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 (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.

Sequential alteration of peanut agglutinin binding-glycoprotein expression during progression of murine mammary neoplasia

“…Mammary mucins (Taylor-Papadimitriou et al, 1990;McKenzie et al, 1990), E-cadherins (Nagafuchi et al, 1987), CD44 (Brown et al, 1991) or betal integrin (Oz et al, 1989) are some of the obvious candidates. There is also an interesting size similarity between a sialylated gp 150 involved in liver metastasis formation by murine leukaemia cells (Benedetto et al, 1989) and the 150 kd glycoprotein sialylated during in vivo passage of mammary D2.OR tumour cells. Sialylation of the latter molecule appeared to be involved in full expression (or derepression?)…”

“…Oncodevelopmental antigens have been detected in breast cancer specimens using monoclonal antibodies specific for blood group related carbohydrates (Feizi, 1985a;Feizi, 1985b;Gooi, 1985a;Gooi, 1985b) and PNA (Springer, 1984). Sialylation of various glycoconjugates correlates with metastatic phenotype in different systems (Benedetto et al, 1989;Bresalier et al, 1990;Corfield et al, 1990;Friedman et al, 1988;Passaniti & Hart, 1988;Dennis et al, 1989). However, there is also evidence indicating that in some systems the expression of non-sialylated structures binding SBA (Buckey et al, 1988) or PNA (Badenoch-Jones et al, 1987;Schirrmacher et al, 1982) is associated with metastasis.…”

Desialylation of metastatic human colorectal carcinoma cells facilitates binding to Kupffer cells

“…Trypsin cleaves glycoproteins from the cell surface while neuraminidase specifically cleaves sialic acids leaving exposed galactose residues. Increasing amounts of sialic acid on the terminal position of N-linked oligosaccharide chains have also been associated with increasing tumorigenic and metastatic potential of tumor cells [9][10][11][12].…”

Tunicamycin Treatment Reduces Intracellular Glutathione Levels: Effect on the Metastatic Potential of the Rhabdomyosarcoma Cell Line S4MH

“…The lectin Triticum vulgare (WGA) binds sialic acid (SA) and chitobiose oligosaccharides [8]. Hyposialylation of membrane glycoproteins in poorly metastatic variants of tumor cells has been proved to occur parallel to loss of reactivity with the lectin WGA [9]. Moreover, non-WGA-reactive tumor cells have been demonstrated to be poorly metastatic [10,11].…”