Effects of altering surface glycoprotein composition on metastatic colonisation potential of murine mammary tumour cells

Abstract

Summary This study has examinied cells from naturally-occurring murine mammary tumours to ascertain whether cell surface glycoproteins play a significant role in colonisation of the lungs after intravenous inoculation. It was found that gel electrophoretic analysis of membrane extracts and lectin adsorption studies (ild inot reve;fl anv consistent differences in dlvconrotein composition of cells from tumours which can heavily colonise the lungs relative to ones from tumours which . innot do so or to cells from pulmonary metastases. Also, alteration of structural and functional properties of surface glycoproteins by treatment with succinylated lectins or with drugs such as tunicamycin and swainsonine, which inhibit glycosylation of membrane proteins, had no specific effects on metastatic colonisation of the lungs. Tunicamycin apparently decreased capability to form experimental metastases but also diminished tumourigenicity on subcutaneous inoculation, although it did not affect tumour cell viability in vitro. This information supports earlier studies from this laboratory involving enzymic digestion of the surface of living tumour cells before inoculation and demonstrates that the pulmonary colonisation capability of these mammary tumour cells can withstand global disorganisation of membrane glycoprotein structure and composition. This implies that either the surface glycoproteins are not important in the colonisation process, or that these tumour cells have great capability for rapid repair of their surfaces. It is concluded that a clear answer to whether surface glycoprotein composition has a decisive role in pulmonary colonisation by these mammary tumour cells requires introduction of stable heritable traits into tumour cell populations by genetic manipulation.

Analysis of cell‐surface sugar receptor expression by neoglycoenzyme binding and adhesion to plastic‐immobilized neoglycoproteins for related weakly and strongly metastatic cell lines of murine tumor model systems

“…The determined enzymatic activity was calculated in fmol with activity graphs, drawn for each individual enzyme preparation. Transformation of the binding data for the neoglycoenzymes to obtain the dissociation constant (K,) and to estimate the number of available binding sites at saturation was performed (Scatchard, 1949). Inhibition con-trols to ascertain the specificity of the protein-carbohydrate interaction were performed at 4°C by pre-incubating the cells for 15 min with 50 pglml homologous or heterologous neoglycoprotein, followed by a co-incubation for 15 min with the neoglycoenzyme.…”