Effects of tunicamycin on B16 metastatic melanoma cell surface glycoproteins and blood-borne arrest and survival properties.
The role of cell surface glycoproteins in determining in vivo blood-borne arrest and survival characteristics of murine melanoma sublines of low (B16-F1) or high (B16-F10) potential to form experimental lung metastases after injection i.v. was assessed after inhibiting tumor cell protein glycosylation with tunicamycin. Incubation of B16-F1 or B16-F10 cells with 0.5 micrograms (or above) tunicamycin per ml for 12 to 36 hr inhibited significantly lung tumor colony formation. Examination of B16 cells in the presence of 0.5 micrograms drug per ml indicated that complex oligosaccharide synthesis was inhibited greater than 90%, while protein synthesis remained at about 50% of the control levels. Tunicamycin induced morphological changes in B16-F1 and B16-F10 cells such as cellular rounding. Cell growth was also inhibited by tunicamycin. These effects were reversible, and B16 cells recovered their normal morphologies and growth rates within 24 hr after removal of the drug. Exposed cell surface protein analyzed by lactoperoxidase-catalyzed 125I iodination-sodium dodecyl sulfate-polyacrylamide gel electrophoresis-autoradiography showed few changes after tunicamycin treatment; however, sialogalactoproteins (detected by the binding of 125I-labeled R. communis agglutinin I to polyacrylamide gels containing desialized B16 cell surface components) were reduced dramatically by the drug. The adhesive properties of untreated and tunicamycin-treated B16 cells were assessed by the binding of 51Cr-labeled B16 cells to endothelial cell monolayers. Tunicamycin-treated B16-F1 and B16-F10 cells adhered at lower rates to endothelial cells such that after 24 to 36 hr of drug (0.5 micrograms/ml) treatment adhesion was almost completely blocked, suggesting that tunicamycin-induced cell surface glycoprotein changes in B16 melanoma cells may interfere with tumor cell-host cell interactions that lead to arrest and survival of blood-borne malignant cells.
D000818:Animals; D001345:Autoradiography; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005944:Glucosamine / Q000031:analogs & derivatives*; D006023:Glycoproteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000556:secondary; D046911:Macromolecular Substances; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D009360:Neoplastic Cells, Circulating; D009844:Oligosaccharides / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology*
D006023:Glycoproteins; D046911:Macromolecular Substances; D009844:Oligosaccharides; D014415:Tunicamycin; D005944:Glucosamine