Control of metastasis by Asn-linked, β1-6 branched oligosaccharides in mouse mammary cancer cells
Control of metastasis by Asn-linked, β1-6 branched oligosaccharides in mouse mammary cancer cells
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DOI：
10.1093/glycob/9.3.235
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发表时间：
1999-03-01
期刊：
影响因子：
4.3
通讯作者：
Chaney, WG
中科院分区：
文献类型：
--
作者：
Seberger, PJ;Chaney, WG
在细胞系和恶性人体组织中的研究已经表明，增加的细胞表面Asn连接的β 1-6（GlcNAc β 1- 6 Man）分支与增加的肿瘤发生和转移特性相关。在该研究中，用含有N-乙酰葡糖胺转移酶V（GlcNAcT-V EC 2.4.1.155）的小鼠cDNA的表达载体转染三种小鼠乳腺癌细胞系，N-乙酰葡糖胺转移酶V是负责在Asn连接的碳水化合物上引发β 1-6分支的糖基转移酶。筛选细胞系对L-PHA的细胞毒性增加，L-PHA是一种对β 1-6分支结构特异性的凝集素。表现出增加的L-PHA细胞毒性的细胞系表达增加水平的β 1-6分支结构。北方印迹检测到在L-PHA敏感细胞系中存在从表达载体转录的GlcNAcT-V。注射到小鼠尾静脉后，相对于对照转染细胞系，细胞表面β 1-6分支增加的转染细胞系形成的肺肿瘤水平升高（P < 0.002）。用凝集素DSA和WGA探测的GlcNAcT-V转染细胞和对照细胞的膜蛋白的Western印迹未显示转染细胞系中聚N-乙酰乳糖胺和唾液酸含量的增加。这些结果表明，由于GlcNAcT-V表达的升高导致的β 1-6分支的特异性增加了转移潜力。
Studies in cell lines and malignant human tissues have shown that increased cell-surface Asn-linked beta 1-6(GlcNAc beta 1-6Man) branching is associated with increased tumorigenic and metastatic properties, In this study, three mouse mammary cancer cell lines were transfected with an expression vector containing the mouse cDNA for N-acetylglucosaminyltransferase V (GlcNAcT-V EC 2.4.1.155), the glycosyltransferase responsible for initiating beta 1-6 branching on Asn-linked carbohydrates. The cell lines were screened for increased cytotoxicity to L-PHA, a lectin specific for beta 1-6 branching structures. Cell lines exhibiting increased L-PHA cytotoxicity expressed increased levels of beta 1-6 branching structures. Northern blots detected the presence of GlcNAcT-V transcribed from the expression vector in the L-PHA sensitive cell lines. After injection into the tail veins of mice, transfected cell lines with increased beta 1-6 branching on the cell surface formed elevated levels of lung tumors relative to control transfected cell lines (P < 0.002). Western blots of membrane proteins from GlcNAcT-V transfected and control cells probed with the lectins DSA and WGA did not show an increase in polyN-acetyllactosamine and sialic acid content in the transfected cell lines. These results demonstrate that a specific increase in beta 1-6 branching due to an elevation in GlcNAcT-V expression increases metastatic potential.