Expression of alpha-GalNAc glycoproteins by breast cancers.
Expression of alpha-GalNAc glycoproteins by breast cancers.
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DOI：
10.1038/bjc.1995.199
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发表时间：
1995-05
影响因子：
8.8
通讯作者：
Leathem, A J
中科院分区：
文献类型：
--
作者：
Brooks, S A;Leathem, A J
已显示，由Hessopomatia凝集素（HPA，标称单糖结合特异性α-GalNAc）识别的复合碳水化合物的表达可预测乳腺癌和其他癌症的不良预后。已经表明HPA结合的预后意义可能是通过识别Tn表位（α-GalNAc-O-丝氨酸/苏氨酸）或血型A抗原（末端α-l->3GalNAc连接到碱性H-抗原，Fuc-alpha-l->2-Gal-beta-l->4（或3）GlcNAc->R）。在这项研究中，使用HPA和两种单克隆抗体-BRIC 66（抗α-GalNAc）和BRIC 111（抗Tn）对终止于α-GalNAc残基的糖蛋白的表达进行了化学分析。在石蜡切片中，74/87（85%）的乳腺癌表达HPA结合配体，而28/87（32%）的BRIC 66结合阳性，25/87（29%）表达Tn。三种标记物的染色模式分布有明显差异。BRIC 66、BRIC 111和HPA与来自乳腺癌匀浆的糖蛋白以及与A血型和Tn阳性糖蛋白在Western印迹中的结合证实了免疫组织化学数据。结果表明，HPA结合在乳腺癌中的预后意义不太可能简单地通过识别血型A抗原或癌细胞上的Tn表位。乳腺癌可能表达一种复杂的相关但不同的聚糖谱，这些聚糖共享相似的末端免疫显性糖GalNAc，这可能与侵袭性生物学行为有关。
The expression of complex carbohydrates recognised by Helix pomatia lectin (HPA, nominal monosaccharide binding specificity alpha-GalNAc) has been shown to predict unfavourable prognosis in breast and other cancers. It has been suggested that the prognostic significance of HPA binding may be through recognition of either Tn epitope (alpha-GalNAc-O-serine/threonine) or blood group A antigen (terminal alpha-1-->3GalNAc attached to the basic H-antigen, Fuc-alpha-1-->2-Gal-beta-1-->4(or 3) GlcNAc-->R). In this study, the expression of glycoproteins terminating in alpha-GalNAc residues was investigated immunohistochemically using HPA and two monoclonal antibodies--BRIC 66 (anti-alpha-GalNAc) and BRIC 111 (anti-Tn). In paraffin sections, 74/87 (85%) of breast cancers expressed HPA-binding ligands, while 28/87 (32%) were positive for BRIC 66 binding and 25/87 (29%) expressed Tn. Distribution of staining patterns were distinctive and different with the three markers. BRIC 66, BRIC 111 and HPA binding to glycoproteins derived from breast cancer homogenates and to blood group A and Tn positive glycoproteins in Western blots confirmed the immunohistochemistry data. The results suggest that the prognostic significance of HPA binding in breast cancer is unlikely to be simply through recognition of blood group A antigen or Tn epitope on cancer cells. Breast cancers may express a complex profile of related but distinct glycans sharing similar terminal immunodominant sugar GalNAc, which may be implicated in aggressive biological behaviour.