Core 2 β1,6-N-acetylglucosaminyltransferases and α1,3-fucosyltransferases regulate the synthesis of O-glycans on selectin ligands on oral cavity carcinoma cells
Core 2 β1,6-N-acetylglucosaminyltransferases and α1,3-fucosyltransferases regulate the synthesis of O-glycans on selectin ligands on oral cavity carcinoma cells
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DOI：
10.1111/j.1600-0463.2001.apm090703.x
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发表时间：
2001-07-01
期刊：
影响因子：
2.8
通讯作者：
Renkonen, R
中科院分区：
文献类型：
--
作者：
Renkonen, J;Räbinä, J;Renkonen, R
选择素依赖性细胞结合在血液循环肿瘤细胞的外渗和转移的产生中具有重要性。用唾液酸化、岩藻糖基化表位修饰的细胞表面糖蛋白，如唾液酸化刘易斯（x）（sLe（x））是选择素的配体。不仅末端sLex部分，而且近端核心结构有助于形成选择素的结合表位。核心2 β 1，6-N-乙酰葡糖胺基转移酶（C2 GnT）和α 1，3-岩藻糖基转移酶（α 1，3-FucT）被认为是选择素配体合成的限速酶。我们分析了口腔上皮癌细胞系，并显示其C2 GnT和α 1，3-FucT的RNA转录本的表达，鉴定了α 1，3-FucT酶活性，并分析了细胞表面sLe（x）表达水平。无论是表达的酶的模式，也没有alpha 1，3-FucT活性直接预测E-选择素的结合能力。但只有sLe（x）表达细胞能与E-选择素结合，而不能与P-选择素结合，从而促进选择素介导的转移。这些结果表明，C2 GnT与α 1，3-Fuc-T的组合有助于选择素介导的口腔癌转移。
Selectin-dependent cell binding has importance in the extravasation of blood-circulating tumor cells and in the generation of metastases. Cell surface glycoproteins; decorated with sialylated, fucosylated epitopes, such as sialyl Lewis(x) (sLe(x)) are ligands for selectins. Not only terminal sLex moieties but also proximal core structures contribute to the formation of binding epitopes for selectins. Core 2 beta1,6-N-acetylglucosaminyltransferases (C2GnT) and alpha1,3-fucosyltransferases (alpha1,3-FucT) have been suggested to be the rate-limiting enzymes in the synthesis of selectin ligands. We analyzed oral cavity epithelial carcinoma cell lines and showed their expression of RNA transcripts for C2GnT and alpha1,3-FucT, identified alpha1,3-FucT enzyme activities, and analyzed the cell surface sLe(x) expression levels. Neither the pattern of expressed enzymes nor the alpha1,3-FucT activity directly predicted the binding capacity of E-selectin. However, only the sLe(x)-expressing cell lines were capable of binding to E-selectin, but not to P-selectin, thus putatively promoting the selectin-mediated metastasis. These findings suggest that C2GnT in combination with alpha1,3-Fuc-T contribute to the selectin-mediated metastasis in oral cavity carcinomas.