Alterations in the glycolipid composition and cellular properties of ovarian carcinoma-derived RMG-1 cells on transfection of the α1,2-fucosyltransferase gene
Alterations in the glycolipid composition and cellular properties of ovarian carcinoma-derived RMG-1 cells on transfection of the α1,2-fucosyltransferase gene
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DOI：
10.1111/j.1349-7006.2005.00005.x
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发表时间：
2005-01-01
期刊：
影响因子：
5.7
通讯作者：
Nozawa, S
中科院分区：
文献类型：
--
作者：
Iwamori, M;Tanaka, K;Nozawa, S
将小鼠 Fut1 和 Fut2 以及人 FUT1 基因转染到人卵巢癌衍生的 RMG-1 细胞中，导致细胞 α1,2-岩藻糖基转移酶活性增加 20-30 倍，并改变糖脂组成，不仅包括岩藻糖基化产物，还包括前体糖脂。虽然globo系列糖脂没有受到转染的显着影响，但RMG-1细胞和转染子中属于乳系列1型链家族的主要糖脂分别是Lc(4)Cer、Lewis a (Le)(a)和Le(b)以及H-1糖脂，这表明Lc(4)Cer对H-1糖脂的岩藻糖基化阻止了进一步修饰转染子中的 Lc(4)Cer 变为 Le(a) 和 Le(b)。此外，RMG-1细胞中的乳系列2型链是Le(x)、NeuAc-nLc(4)Cer和NeuAc-Le(X)，而转染子中的乳系列2型链是Le(X)和Le(Y)，表明nLc(4)Cer和Le(X)的唾液酸化受到Le(X)岩藻糖基化增加的限制。结果，转染子中唾液酸酶释放的唾液酸量减少至 RMG-1 细胞的 70%，并且发现转染子的几种膜介导现象（例如癌细胞与间皮细胞之间的细胞间相互作用，以及抗癌药物 5-氟尿嘧啶存在下的细胞活力）与 RMG-1 细胞相比有所增加。这些发现表明细胞表面碳水化合物与癌细胞的生物学特性有关，包括细胞间粘附和耐药性。
Transfection of the mouse Fut1 and Fut2 and human FUT1 genes into human ovarian carcinoma-derived RMG-1 cells resulted in 20-30-fold increases in cellular alpha1,2-fucosyltransferase activity, and in alteration of the glycolipid composition, including not only fucosylated products, but also precursor glycolipids. Although globo-series glycolipids were not significantly affected by the transfection, the major glycolipids belonging to the lacto-series type 1 chain family in RMG-1 cells and the transfectants were the Lc(4)Cer, Lewis a (Le)(a) and Le(b), and H-1 glycolipids, respectively, suggesting that fucosylation of Lc(4)Cer to the H-1 glycolipid prevents the further modification of Lc(4)Cer to Le(a) and Le(b) in the transfectants. Also, the lacto-series type 2 chains in RMG-1 cells were Le(x), NeuAc-nLc(4)Cer and NeuAc-Le(X), and those in the transfectants were Le(X) and Le(Y), indicating that the sialylation of nLc(4)Cer and Le(X) is restricted by increased fucosylation of Le(X). As a result, the amount of sialic acid released by sialidase from the transfectants decreased to 70% of that from RMG-1 cells, and several membrane-mediated phenomena, such as the cell-to-cell interaction between cancer cells and mesothelial cells, and the cell viability in the presence of an anticancer drug, 5-fluorouracil, for the transfectants was found to be increased in comparison to that for RMG-1 cells. These findings indicate that cell surface carbohydrates are involved in the biological properties, including cell-to-cell adhesion and drug resistance, of cancer cells.