Ogata S, Ho I, Chen A, Dubois D, Maklansky J, Singhal A, Hakomori S, Itzkowitz S H
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Cancer Res. 1995 May 1;55(9):1869-74.
Immunohistochemical studies have indicated that sialylated carbohydrate antigens such as sialyl-Tn, sialyl-Le(a), and sialyl-Le(x) are expressed in a tumor-associated fashion in human colon. Since sialic acid residues are O-acetylated more extensively in normal colonic epithelium than in colon cancer cells, we examined whether deacetylation of colonic tissues might enable monoclonal antibodies to recognize these tumor-associated sialylated antigens. In normal colon, deacetylation turned most cases (82%) positive with anti-sialyl-Tn mAb TKH2; and in colon cancers, it increased the number of TKH2-positive cells. Sialyl-Le(a) and sialyl-Le(x) detection was also increased after deacetylation of normal and malignant colonic tissues so that the frequency of positive cases in normal tissues was similar to that in the cancers. However, in the stomach and pancreas, the same treatment rarely increased the detection of the sialylated epitopes in normal or cancerous tissues. Thus, the same sialylated epitopes can be expressed in a tumor-associated fashion by different mechanisms in different gastrointestinal organs; in the colon, these antigens are constitutively expressed and O-acetylated, whereas in the upper gastrointestinal tract, they are rarely O-acetylated, suggesting that other mechanisms such as differences in glycosylation account for the cancer-associated expression.
免疫组织化学研究表明,唾液酸化碳水化合物抗原,如唾液酸化-Tn、唾液酸化-Le(a)和唾液酸化-Le(x),在人类结肠中以肿瘤相关的方式表达。由于正常结肠上皮细胞中的唾液酸残基比结肠癌细胞中的O-乙酰化程度更高,我们研究了结肠组织的脱乙酰化是否能使单克隆抗体识别这些肿瘤相关的唾液酸化抗原。在正常结肠中,脱乙酰化使大多数病例(82%)用抗唾液酸化-Tn单克隆抗体TKH2检测呈阳性;在结肠癌中,它增加了TKH2阳性细胞的数量。正常和恶性结肠组织脱乙酰化后,唾液酸化-Le(a)和唾液酸化-Le(x)的检测也增加,因此正常组织中的阳性病例频率与癌症中的相似。然而,在胃和胰腺中,相同的处理很少增加正常或癌组织中唾液酸化表位的检测。因此,相同的唾液酸化表位在不同的胃肠器官中可通过不同机制以肿瘤相关的方式表达;在结肠中,这些抗原组成性表达并O-乙酰化,而在上消化道中,它们很少O-乙酰化,这表明糖基化差异等其他机制解释了与癌症相关的表达。