Irimura T, Gonzalez R, Nicolson G L
Cancer Res. 1981 Sep;41(9 Pt 1):3411-8.
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.
在用衣霉素抑制肿瘤细胞蛋白质糖基化后，评估了细胞表面糖蛋白在决定静脉注射后形成实验性肺转移潜能低（B16 - F1）或高（B16 - F10）的小鼠黑色素瘤亚系在体内血行滞留和存活特征方面的作用。将B16 - F1或B16 - F10细胞与每毫升0.5微克（或更高浓度）衣霉素孵育12至36小时，可显著抑制肺肿瘤集落形成。在每毫升含0.5微克药物的条件下对B16细胞进行检测表明，复合寡糖合成被抑制超过90%，而蛋白质合成维持在对照水平的约50%。衣霉素诱导B16 - F1和B16 - F10细胞发生形态变化，如细胞变圆。细胞生长也受到衣霉素抑制。这些作用是可逆的，去除药物后24小时内，B16细胞恢复其正常形态和生长速率。通过乳过氧化物酶催化的125I碘化 - 十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳 - 放射自显影分析暴露的细胞表面蛋白，发现衣霉素处理后变化不大；然而，药物使唾液酸糖蛋白（通过125I标记的蓖麻凝集素I与含去唾液酸化B16细胞表面成分的聚丙烯酰胺凝胶结合检测）显著减少。通过51Cr标记的B16细胞与内皮细胞单层的结合来评估未处理和经衣霉素处理的B16细胞的黏附特性。经衣霉素处理的B16 - F1和B16 - F10细胞与内皮细胞的黏附率较低，以至于在药物（0.5微克/毫升）处理24至36小时后，黏附几乎完全被阻断，这表明衣霉素诱导的B16黑色素瘤细胞表面糖蛋白变化可能干扰肿瘤细胞与宿主细胞的相互作用，而这种相互作用导致血行转移恶性细胞的滞留和存活。
