Reduced cell adhesion to fibronectin and laminin is associated with altered glycosylation of beta 1 integrins in a weakly metastatic glycosylation mutant.
A weakly metastatic wheat-germ-agglutinin-resistant mutant Wa4-b1 was previously shown to be less adherent to endothelial cell extracellular matrix than the more metastatic parental B-16 melanoma cells. This report describes reduced adhesion and spreading of Wa4-b1 cells on the cell-binding domain of fibronectin (CBD) and laminin (LN). Cell surface receptors which mediate such interactions are members of the integrin family of membrane glycoproteins. An antibody that recognizes the beta 1 integrin subunit inhibited spreading on both the CBD and LN. The integrins of the mutant cells immunoprecipitated by the antibody appeared to be structurally altered, showing a greater electrophoretic mobility. The mobility difference between the parent and the mutant receptors was abolished following removal of the glycan moieties of the receptors enzymatically using glycopeptidase F, or chemically using trifluoromethanesulfonic acid, suggesting that the structural alteration of the mutant receptors is in glycosylation. The altered receptors may be responsible for the observed decrease in cell adhesion and spreading of the mutant cells to the CBD and LN. Such a decrease in Wa4-b1 cell interaction with extracellular matrix components may play a role in their decreased metastatic potential.
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Division of Nuclear Medicine, Stanford University, CA.
Campbell
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Tao
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D000818:Animals; D002448:Cell Adhesion; D005353:Fibronectins / Q000502:physiology*; D006031:Glycosylation; D006801:Humans; D016023:Integrins; D007797:Laminin / Q000502:physiology*; D008546:Melanoma, Experimental / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009362:Neoplasm Metastasis; D011971:Receptors, Immunologic / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic