The role of glycoconjugates in metastatic melanoma blood-borne arrest and cell surface properties.
The role of glycoconjugates in cell surface and blood-borne implantation properties of murine metastatic melanoma sublines of low (B16-F1) or high (B16-F10) potential to colonize lungs was investigated by treating melanoma cells with the antibiotic tunicamycin. This drug prevents glycosylation of glycoproteins by inhibiting the formation of lipid-linked oligosaccharide precursors. The degree of tunicamycin-mediated modifications in glycoproteins was assessed by monitoring the decrease in cell surface sialogalactoproteins by binding of 125I-labeled Ricinus communis agglutinin I. Scanning electron microscopy of tunicamycin-treated B16-F1 and B16-F10 cells showed morphologic changes such as cell rounding and formation of numerous surface blebs. Tunicamycin-treated B16-F1 and B16-F10 cells lost their lung colonization abilities when injected intravenously into C57BL/6 mice, concomitant with lowered rates of adhesion to endothelial cell monolayers, endothelial extracellular matrix (basal lamina), and polyvinyl-immobilized fibronectin in vitro, suggesting that this drug inhibits experimental metastasis by modifying the surface glycoproteins involved in determining the adhesive properties of malignant cells.
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D005260:Female; D005944:Glucosamine / Q000031:analogs & derivatives*; D006023:Glycoproteins / Q000502:physiology*; D008175:Lung Neoplasms / Q000648:ultrastructure; D008545:Melanoma / Q000503:physiopathology*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000648:ultrastructure; D014415:Tunicamycin / Q000494:pharmacology*
D006023:Glycoproteins; D014415:Tunicamycin; D005944:Glucosamine