BETA-1-6 BRANCHING OF ASN-LINKED OLIGOSACCHARIDES IS DIRECTLY ASSOCIATED WITH METASTASIS
BETA-1-6 BRANCHING OF ASN-LINKED OLIGOSACCHARIDES IS DIRECTLY ASSOCIATED WITH METASTASIS
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DOI：
10.1126/science.2953071
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发表时间：
1987-05-01
期刊：
影响因子：
56.9
通讯作者：
KERBEL, RS
中科院分区：
文献类型：
--
作者：
DENNIS, JW;LAFERTE, S;KERBEL, RS
肿瘤转化与细胞表面碳水化合物的多种结构变化有关，最显著的是唾液酸化增加和复合型天冬酰胺（Asn）连接的寡糖（即，-GlcNAc β 1 - 6 Man α 1 - 6 Man β 1-）的β 1 -6连接分支。然而，很少有人知道有关的糖蛋白或如何这些转化相关的变化，寡糖生物合成可能会影响恶性表型。这里报道了细胞表面糖蛋白gp 130是增加的β 1 -6-连接分支的主要靶点，并且这些寡糖结构的表达与细胞的转移潜能直接相关。选择在β 1 -6 GlcNAc转移酶V活性和原位转移潜力方面都有缺陷的转移性肿瘤细胞系的糖基化突变体。此外，在非转移性鼠乳腺癌的克隆中β 1 -6分支增加的诱导与转移潜能的获得强烈相关。结果表明，gp 130上复合型寡糖的β 1 -6-连接分支的增加可能是与增加的转移潜能相关的肿瘤进展的重要特征。
Neoplastic transformation has been associated with a variety of structural changes in cell surface carbohydrates, most notably increased sialylation and .beta.1-6-linked branching of complex-type asparagine (Asn)-linked oligosaccharides (that is, -GlcNAc.beta.1-6Man.alpha.1-6Man.beta.1-). However, little is known about the relevant glycoproteins or how these transformation-related changes in oligosaccharide biosynthesis may affect the malignant phenotype. Here it is reported that a cell surface glycoprotein, gp130, is a major target of increased .beta.1-6-linked branching and that the expression of these oligosaccharide structures is directly related to the metastatic potential of the cells. Glycosylation mutants of a metastatic tumor cell line were selected that are deficient in both .beta.1-6 GlcNAc transferase V activity and metastatic potential in situ. Moreover, induction of increased .beta.1-6 branching in clones of a nonmetastatic murine mammary carcinoma correlated strongly with acquisition of metastatic potential. The results indicate that increased .beta.1-6-linked branching of complex-type oligosaccharides on gp130 may be an important feature of tumor progression related to increased metastatic potential.