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The role of glycoconjugates in metastatic melanoma blood-borne arrest and cell surface properties

Tatsuro Irimura, Garth L. Nicolson

Abstract: The role of glycoconjugates in cell surface and blood‐borne implantation properties of murine metastatic melanoma sublines of low (B16‐F1) or high (B 16‐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.
Keywords: adhesion / blood‐borne implantation / extracellular matrix / glycoprotein / melanoma metastasis / tunicamycin / lectin

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