Reduced glycosylation of α-dystroglycans on carcinoma cells contributes to formation of highly infiltrative histological patterns in prostate cancer.
Reduced glycosylation of α-dystroglycans on carcinoma cells contributes to formation of highly infiltrative histological patterns in prostate cancer.
复制标题
DOI：
10.1002/pros.21330
复制
发表时间：
2011-08-01
期刊：
影响因子：
2.8
通讯作者：
Nakayama, Jun
中科院分区：
文献类型：
--
作者：
Shimojo, Hisashi;Kobayashi, Motohiro;Kamigaito, Takayuki;Shimojo, Yasuyo;Fukuda, Minoru;Nakayama, Jun
α-肌营养不良聚糖（DG）携带与层粘连蛋白结合的聚糖链，因此不仅在骨骼肌而且在各种上皮细胞的稳态中起作用。糖基化的丧失在肿瘤的发生发展中起重要作用，特别是在癌细胞的脱离和迁移中。我们以前报道过，α-DG的糖基化，但不是α-DG核心蛋白本身的水平，在前列腺癌中减少。在这项研究中，我们研究了α-DG上层粘连蛋白结合聚糖的减少与肿瘤细胞分化程度和/或浸润特性之间的关系，如Gleason分级系统所评估的。采用IIH 6和6C 1抗体对146例具有不同Gleason评分的前列腺癌活检标本进行免疫组织化学分析，IIH 6和6C 1抗体分别识别α-DG和α-DG核心蛋白上的层粘连蛋白结合聚糖。采用免疫荧光双染色法检测α-DG和层粘连蛋白的共定位，并确定哪种上皮细胞表达α-DG上的层粘连蛋白结合聚糖。α-DG糖基化的减少，而不是α-DG核心蛋白的丢失，与更高的Gleason模式相关。在癌细胞与基底膜的界面处减少最明显。此外，在非肿瘤性前列腺中，层粘连蛋白结合聚糖主要在基底细胞的基底外侧表面上表达。层粘连蛋白结合聚糖在α-DG上的表达减少可能有助于前列腺癌细胞高度浸润行为的形成。癌组织中层粘连蛋白结合聚糖的大量减少可能部分归因于预先存在的基底细胞的消失。
α-Dystroglycan (DG) carries glycan chains that bind to laminin and thus function in homeostasis of not only skeletal muscle but also of various epithelial cells. Loss of glycosylation has been suggested to play important roles in tumor development, particularly in detachment and migration of carcinoma cells. We previously reported that glycosylation of α-DG, but not levels of α-DG core protein itself, is reduced in prostate carcinoma. In this study, we investigate the association between reduction of laminin-binding glycans on α-DG and the degree of tumor cell differentiation and/or infiltrative properties, as assessed by the Gleason grading system. Immunohistochemical analysis of 146 biopsy specimens of prostate adenocarcinoma with various Gleason scores was carried out employing IIH6 and 6C1 antibodies, which recognize laminin-binding glycans on α-DG and α-DG core proteins, respectively. Double immunofluorescence staining was performed to evaluate colocalization of α-DG and laminin, and to determine which types of epithelial cells express laminin-binding glycans on α-DG. Reduction of α-DG glycosylation, rather than loss of α-DG core protein, was correlated with higher Gleason patterns. Reduction was most conspicuous at the interface between carcinoma cells and the basement membrane. In addition, in non-neoplastic prostate glands, laminin-binding glycans were expressed predominantly on the basolateral surface of basal cells. Reduced expression of laminin-binding glycans on α-DG may contribute to formation of highly infiltrative behavior of prostate carcinoma cells. Substantial reduction of laminin-binding glycans in carcinoma tissue could be partly ascribed to disappearance of pre-existing basal cells.
登录
查看更多内容
DOI：
10.1073/pnas.0904515106
发表时间：
2009-07-21
影响因子：
11.1
作者：
Bao, Xingfeng;Kobayashi, Motohiro;Fukuda, Minoru
通讯作者：
Fukuda, Minoru
影响因子：
5.6
作者：
Sgambato, A.;De Paola, B.;Cittadini, A.
通讯作者：
Cittadini, A.
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
4.8
作者：
de Bernabe, Daniel Beltran-Valero;Inamori, Kei-ichiro;Campbell, Kevin P.
通讯作者：
Campbell, Kevin P.
影响因子：
6
作者：
Sgambato, A;Migaldi, M;Cittadini, A
通讯作者：
Cittadini, A