Bolscher J G, Schallier D C, van Rooy H, Storme G A, Smets L A
Division of Cell Biology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam.
Cancer Res. 1988 Feb 15;48(4):977-82.
The effect of the alkyl lysophospholipid racemic-1-O-octadecyl-2-O-methyl glycero-3-phosphocholine on the expression of cell surface carbohydrates of four matched pairs of normal and malignant cells was studied using chromatographic techniques. After treatment with alkyl lysophospholipid, glycopeptides proteolytically derived from normal and malignant cells displayed a shift in the size distribution profiles obtained by gel filtration. These drug-induced changes in molecular weight distribution were expressed most strongly in untransformed cells and resembled the carbohydrate alterations found after their malignant transformation. Desialylation abolished the effect of alkyl lysophospholipid, thus suggesting an increased amount of sialic acid in the surface carbohydrates of drug-treated cells. Chromatography of glycopeptides on concanavalin A-Sepharose, Ricinus communis agglutinin I-agarose, and Bio-Gel P-4 columns excluded a higher degree of branching but suggested addition of extra terminal sialic acid residues as the major cause of the observed alterations. Alkyl lysophospholipid stimulated glycoprotein sialylation of normal cells to the level observed in malignant cells, thus inducing a "malignant-like" surface phenotype. The drug-induced carbohydrate changes in normal chick heart tissue prevented its being invaded by tumor cells when tested in an organotypic assay. The alkyl lysophospholipid thus appears to modulate in a nontoxic fashion the expression of surface molecules implicated in various cellular interactions including invasiveness.
使用色谱技术研究了烷基溶血磷脂消旋-1-O-十八烷基-2-O-甲基甘油-3-磷酸胆碱对四对匹配的正常细胞和恶性细胞表面碳水化合物表达的影响。用烷基溶血磷脂处理后,从正常细胞和恶性细胞中通过蛋白水解得到的糖肽在凝胶过滤获得的大小分布图谱上出现了偏移。这些药物诱导的分子量分布变化在未转化细胞中表现最为强烈,并且类似于它们恶性转化后发现的碳水化合物改变。去唾液酸化消除了烷基溶血磷脂的作用,因此表明药物处理细胞表面碳水化合物中的唾液酸含量增加。糖肽在伴刀豆球蛋白A-琼脂糖、蓖麻凝集素I-琼脂糖和Bio-Gel P-4柱上的色谱分析排除了更高程度的分支,但表明添加额外的末端唾液酸残基是观察到的改变的主要原因。烷基溶血磷脂将正常细胞的糖蛋白唾液酸化刺激到恶性细胞中观察到的水平,从而诱导出“恶性样”表面表型。当在器官型试验中进行测试时,药物诱导的正常鸡心脏组织碳水化合物变化阻止了其被肿瘤细胞侵袭。因此,烷基溶血磷脂似乎以无毒方式调节参与包括侵袭性在内的各种细胞相互作用的表面分子的表达。