Ho J J, Chung Y S, Fujimoto Y, Bi N, Ryan W, Yuan S Z, Byrd J C, Kim Y S
Gastrointestinal Research Laboratory, Veterans Administration Medical Center, San Francisco, California 94121.
Cancer Res. 1988 Jul 15;48(14):3924-31.
The antigenic determinant recognized by monoclonal antibody SPan-1 is greatly elevated in sera of patients with pancreatic cancer but not in sera of normal individuals. Here we describe the mucin-like characteristics of the SPan-1 antigen isolated from culture medium and xenografts of the human pancreatic cancer cell line SW-1990. YPan-1, another pancreatic cancer associated monoclonal antibody, also reacts with the SPan-1 antigen. The SPan-1/YPan-1 antigens have densities of 1.4-1.5 g/ml and elute in the void volume of Sepharose CL-2B columns. They are resistant to degradation by chondroitinase ABC, nitrous acid, and hyaluronidase but susceptible to protease digestion and reductive beta-elimination. All these characteristics suggest that the SPan-1 and YPan-1 determinants are carried on mucinous antigens. Both SPan-1 and YPan-1 immunoreactivities are unaffected by boiling or by alkylation and reduction of the mucins while they are abolished by mild periodate oxidation or neuraminidase and are markedly decreased by wheat germ agglutinin. Thus, their antigenic determinants are composed principally of carbohydrates with sialic acid, an absolute requirement for reactivity. However, the epitope specificities of SPan-1 and YPan-1 are different since YPan-1 does not compete with SPan-1 for binding to antigen. Moreover, YPan-1 and SPan-1 can be distinguished from several other sialic acid requiring, cancer associated antibodies such as B72.3, CSLEX-1, DU-PAN-2, OC-125, and 19-9 by either their epitope characteristics or their tissue reactivity patterns.
单克隆抗体SPan-1识别的抗原决定簇在胰腺癌患者血清中显著升高,而在正常个体血清中则不然。在此,我们描述了从人胰腺癌细胞系SW-1990的培养基和异种移植物中分离出的SPan-1抗原的黏蛋白样特征。另一种与胰腺癌相关的单克隆抗体YPan-1也与SPan-1抗原发生反应。SPan-1/YPan-1抗原的密度为1.4 - 1.5 g/ml,在琼脂糖CL-2B柱的空体积中洗脱。它们对软骨素酶ABC、亚硝酸和透明质酸酶的降解具有抗性,但易受蛋白酶消化和还原性β-消除的影响。所有这些特征表明,SPan-1和YPan-1决定簇存在于黏蛋白抗原上。SPan-1和YPan-1的免疫反应性不受煮沸或黏蛋白的烷基化和还原的影响,而在温和的高碘酸盐氧化或神经氨酸酶处理后被消除,并且被麦胚凝集素显著降低。因此,它们的抗原决定簇主要由含有唾液酸的碳水化合物组成,唾液酸是反应性的绝对必需条件。然而,SPan-1和YPan-1的表位特异性不同,因为YPan-1不与SPan-1竞争结合抗原。此外,YPan-1和SPan-1可以通过它们的表位特征或组织反应模式与其他几种需要唾液酸的、与癌症相关的抗体如B72.3、CSLEX-1、DU-PAN-2、OC-125和19-9区分开来。