Gabius H J, Bahn H, Holzhausen H J, Knolle J, Stiller D
Institut für Pharmazeutische Chemie, Abteilung Glykobiochemie und Angewandte Tumorlektinologie, Philipps Universität, Marburg F.R.G.
Anticancer Res. 1992 May-Jun;12(3):987-92.
Chemical conjugation of carbohydrate derivatives to a labelled carrier protein makes it possible to monitor the presence of specific sugar-dependent binding to routinely processed tissue sections. Different levels of cytoplasmic staining were observed in normal urothelium for the applied probes that expose a beta-D-galactoside, alpha- or beta-N-acetyl-D-galactosaminide, beta-N-acetyl-D-glucosaminide, alpha-D-mannoside, alpha-L-fucoside or a-D-glucoside, respectively. These moieties are crucial parts of the recognition sites in cellular glycoconjugates for plant lectins. The extent of staining invariably increased from the basal to the luminal cell layer. No nuclear staining was observed. Within the 18 cases of bladder lesions studied, the appearance of nuclear staining was characteristic of transitional cell carcinoma, its correlation to the histologic grade being dependent on the type of neoglycoprotein. Cytoplasmic staining revealed at least two patterns of grade-dependent variations, namely rather constant expression for lactose-mannose-, fucose- and maltose-specific sites and an initial increased followed by a loss of binding activity at the highest level of cellular atypia for the other three types of probe. Intratumoral heterogeneity was especially visible in tumors of this group. Interestingly, the known positive correlation of presence of the Thomsen-Frieden rich antigen with the level of cellular atypia, monitored with peanut agglutinin, could be extended to the expression of respective receptor sites, which was experimentally feasible due to the synthesis of this disaccharide structure and its immobilization to the carrier protein.
将碳水化合物衍生物与标记的载体蛋白进行化学偶联，使得监测常规处理的组织切片中特定糖依赖性结合的存在成为可能。在所应用的分别暴露β-D-半乳糖苷、α-或β-N-乙酰-D-半乳糖胺、β-N-乙酰-D-葡糖胺、α-D-甘露糖苷、α-L-岩藻糖苷或α-D-葡萄糖苷的探针中，在正常尿路上皮中观察到不同程度的细胞质染色。这些部分是细胞糖缀合物中植物凝集素识别位点的关键部分。染色程度总是从基底细胞层到腔面细胞层增加。未观察到核染色。在研究的18例膀胱病变中，核染色的出现是移行细胞癌的特征，其与组织学分级的相关性取决于新糖蛋白的类型。细胞质染色揭示了至少两种分级依赖性变化模式，即乳糖-甘露糖、岩藻糖和麦芽糖特异性位点的表达相当恒定，而其他三种探针在细胞异型性最高水平时结合活性先增加后丧失。肿瘤内异质性在该组肿瘤中尤为明显。有趣的是，用花生凝集素监测到的汤姆森-弗里德富含抗原的存在与细胞异型性水平之间已知的正相关性，可以扩展到相应受体位点的表达，由于这种二糖结构的合成及其固定到载体蛋白上，这在实验上是可行的。
