Huang J, Byrd J C, Yoon W H, Kim Y S
Gastrointestinal Research Laboratory, VA Medical Center, San Francisco, CA.
Oncol Res. 1992;4(11-12):507-15.
Many cancer-associated antigens are present on mucin glycoproteins. These include peripheral antigens such as sialyl Lea and sialyl Lex and core region carbohydrate antigens such as T, Tn, and Sialyl Tn. We have recently described an inhibitor of mucin glycosylation, benzyl-alpha-GalNAc. The purpose of this study was to determine its effect on expression of mucin carbohydrate antigens. HM7 colon cancer cells were treated for 2 days in culture with 2 mM benzyl-alpha-GalNAc. This treatment did not affect viability or doubling time, but inhibited synthesis of [3H]glucosamine-labeled mucins. There was also secretion of benzyl-oligosaccharides and a decrease in the proportion of long oligosaccharides on 3H-labeled mucins. Mucins were purified from spent media by gel filtration and assayed for binding of monoclonal antibodies and lectins. Mucins from benzyl-alpha-GalNAc-treated cells had increased binding of peanut agglutinin (specific for T antigen, Gal beta 3GalNAc) and Vicia villosa agglutinin B4 (specific for Tn antigen, GalNAc alpha-Thr/Ser), but decreased binding of monoclonal antibodies 19-9, SNH3, and 91.9H (specific for sialyl Lea, sialyl Lex, and sulfomucin, respectively). Treatment of the cells with benzyl-alpha-GalNAc also decreased their binding to E-selectin (ELAM-1), which recognizes sialyl Lea and sialyl Lex. Thus, benzyl-alpha-GalNAc treatment, which decreases the level of peripheral carbohydrate carbohydrate antigens on mucins with accumulation of core region antigens, may be useful in modifying the immunological and biological properties of colon cancer cells.
许多癌症相关抗原存在于黏蛋白糖蛋白上。这些包括外周抗原，如唾液酸化Lea和唾液酸化Lex，以及核心区域碳水化合物抗原，如T、Tn和唾液酸化Tn。我们最近描述了一种黏蛋白糖基化抑制剂，苄基-α-乙酰半乳糖胺。本研究的目的是确定其对黏蛋白碳水化合物抗原表达的影响。HM7结肠癌细胞在培养中用2 mM苄基-α-乙酰半乳糖胺处理2天。这种处理不影响细胞活力或倍增时间，但抑制了[3H]葡萄糖胺标记的黏蛋白的合成。还分泌了苄基寡糖，并且3H标记的黏蛋白上长寡糖的比例降低。通过凝胶过滤从用过的培养基中纯化黏蛋白，并测定其与单克隆抗体和凝集素的结合。来自苄基-α-乙酰半乳糖胺处理细胞的黏蛋白与花生凝集素（对T抗原，Galβ3GalNAc特异）和绒毛豆凝集素B4（对Tn抗原，GalNAcα-Thr/Ser特异）的结合增加，但与单克隆抗体19-9、SNH3和91.9H（分别对唾液酸化Lea、唾液酸化Lex和硫黏蛋白特异）的结合减少。用苄基-α-乙酰半乳糖胺处理细胞也降低了它们与E-选择素（ELAM-1）的结合，E-选择素识别唾液酸化Lea和唾液酸化Lex。因此，苄基-α-乙酰半乳糖胺处理可降低黏蛋白外周碳水化合物抗原水平并积累核心区域抗原，可能有助于改变结肠癌细胞的免疫和生物学特性。
