Comprehensive Glycomics of a Multistep Human Brain Tumor Model Reveals Specific Glycosylation Patterns Related to Malignancy.
Comprehensive Glycomics of a Multistep Human Brain Tumor Model Reveals Specific Glycosylation Patterns Related to Malignancy.
复制标题
DOI：
10.1371/journal.pone.0128300
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Shinohara Y
中科院分区：
文献类型：
--
作者：
Furukawa J;Tsuda M;Okada K;Kimura T;Piao J;Tanaka S;Shinohara Y
癌细胞经常表达不同水平的聚糖和/或与正常细胞表达的聚糖具有根本不同的结构，因此阐明和操纵这些糖基化可能为癌症治疗提供有益的方法。然而，糖基化改变与因果遗传改变之间的关系仅部分被理解。在这里，我们采用了一种独特的方法，将综合糖糖分析应用于先前描述的多步骤肿瘤发生模型。通过连续导入hTERT、SV40ER、H-RasV12和myrAKT来转化正常的人类星形胶质细胞，从而模拟人类脑肿瘤的I-IV级。我们对来自细胞表面三大类糖缀合物（糖蛋白上的N-和o -聚糖以及鞘糖脂）的160多种聚糖进行了定量研究，并系统地鉴定了与恶性肿瘤相关的特异性糖基化模式。依次导入hTERT、SV40ER、H-RasV12和myrAKT导致(i) pauci-甘露糖/单天线型n -聚糖和GD3 （hTERT）的时间表达；（ii）从神经节到全球系列鞘糖脂的转换和Neu5Gc （hTERT和SV40ER）的出现；（iii）分切GlcNAc残基、α2,6-唾液酰化和阶段特异性胚胎抗原-4的时间表达，同时抑制核心2 - o -聚糖生物合成（hTERT、SV40ER和Ras）；（iv） （neo）乳酸系列鞘糖脂和聚焦n -聚糖（hTERT、SV40ER、Ras和AKT）的表达增加。这些顺序的和短暂的糖糖改变可能对肿瘤分级诊断和肿瘤预后有用，也可用于预测治疗反应。
Cancer cells frequently express glycans at different levels and/or with fundamentally different structures from those expressed by normal cells, and therefore elucidation and manipulation of these glycosylations may provide a beneficial approach to cancer therapy. However, the relationship between altered glycosylation and causal genetic alteration(s) is only partially understood. Here, we employed a unique approach that applies comprehensive glycomic analysis to a previously described multistep tumorigenesis model. Normal human astrocytes were transformed via the serial introduction of hTERT, SV40ER, H-RasV12, and myrAKT, thereby mimicking human brain tumor grades I-IV. More than 160 glycans derived from three major classes of cell surface glycoconjugates (N- and O-glycans on glycoproteins, and glycosphingolipids) were quantitatively explored, and specific glycosylation patterns related to malignancy were systematically identified. The sequential introduction of hTERT, SV40ER, H-RasV12, and myrAKT led to (i) temporal expression of pauci-mannose/mono-antennary type N-glycans and GD3 (hTERT); (ii) switching from ganglio- to globo-series glycosphingolipids and the appearance of Neu5Gc (hTERT and SV40ER); (iii) temporal expression of bisecting GlcNAc residues, α2,6-sialylation, and stage-specific embryonic antigen-4, accompanied by suppression of core 2 O-glycan biosynthesis (hTERT, SV40ER and Ras); and (iv) increased expression of (neo)lacto-series glycosphingolipids and fucosylated N-glycans (hTERT, SV40ER, Ras and AKT). These sequential and transient glycomic alterations may be useful for tumor grade diagnosis and tumor prognosis, and also for the prediction of treatment response.
登录
查看更多内容
DOI：
10.1111/j.1432-1033.1995.607_2.x
发表时间：
1995-10-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
BROCKHAUSEN, I;YANG, JM;TAYLORPAPADIMITRIOU, J
通讯作者：
TAYLORPAPADIMITRIOU, J
影响因子：
3.1
作者：
Dall'Olio, Fabio;Malagolini, Nadia;Chiricolo, Mariella
通讯作者：
Chiricolo, Mariella
影响因子：
158.5
作者：
Hegi, ME;Diserens, A;Stupp, R
通讯作者：
Stupp, R
DOI：
10.1073/pnas.1007290108
发表时间：
2010-12-28
影响因子：
11.1
作者：
Liang, Yuh-Jin;Kuo, Huan-Hsien;Yu, John
通讯作者：
Yu, John
DOI：
10.1097/pai.0b013e3181e3bf0d
发表时间：
2010-12-01
影响因子：
1.6
作者：
Aoyanagi, Eiko;Sasai, Ken;Tanaka, Shinya
通讯作者：
Tanaka, Shinya