Biological significance of cancer-associated sialyl-Tn antigen: Modulation of malignant phenotype in gastric carcinoma cells

Biological significance of cancer-associated sialyl-Tn antigen: Modulation of malignant phenotype in gastric carcinoma cells
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DOI:
10.1016/j.canlet.2006.08.010
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发表时间:
2007-05-08
期刊:
影响因子:
9.7
通讯作者:
Reis, Celso A.
Reis, Celso A.
中科院分区:
医学1区
文献类型:
--
作者:
Pinho, Sandra;Marcos, Nuno T.;Reis, Celso A.

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癌细胞中异常糖基化途径的激活导致唾液酰- tn抗原的形成,阻断正常的碳水化合物链延伸。唾液酰- tn抗原在正常组织中很少表达,但在多种癌中表达异常,是预后不良的标志。虽然唾液酰- tn的临床意义已被很好地表征,但这种聚糖的功能作用及其对癌症进展的贡献仍有待阐明。本研究评估了sialyl-Tn对细胞周期、凋亡、肌动蛋白细胞骨架动力学、ECM组分的粘附和运动、细胞-细胞聚集和侵袭等过程的调节能力。sialyl-Tn的从头表达导致胃癌细胞的形态和细胞行为发生重大变化,这些变化通过特异性抗体阻断而恢复。Sialyl-Tn抗原能够调节一种恶性表型,诱导更具有攻击性的细胞行为,如细胞-细胞聚集减少和ECM粘附、迁移和侵袭增加。2006爱思唯尔爱尔兰有限公司版权所有。
The activation of an abnormal glycosylation pathway in cancer cells leads to the formation of the sialyl-Tn antigen, blocking regular carbohydrate chain elongation. Sialyl-Tn antigen is rarely expressed in normal tissues but is aberrantly expressed in a variety of carcinomas, where it constitutes a marker of poor prognosis. Although the clinical significance of sialyl-Tn is well characterized, a functional role for this glycan and its contribution to cancer progression remain to be elucidated. This study evaluates the capability of sialyl-Tn to modify processes like cell cycle, apoptosis, actin cytoskeleton dynamics, adhesion and motility on ECM components, cell-cell aggregation and invasion. De-novo expression of sialyl-Tn leads to major morphological and cell behavior alterations in gastric carcinoma cells which were reverted by specific antibody blockage. Sialyl-Tn antigen is able to modulate a malignant phenotype inducing a more aggressive cell behavior, such as decreased cell-cell aggregation and increased ECM adhesion, migration and invasion. (c) 2006 Elsevier Ireland Ltd. All rights reserved.