Ho J J, Norton K, Chung Y S, Kim Y S
Gastrointestinal Research Laboratory (151M2), Veterans' Affairs Medical Center, San Francisco, CA 94121.
Oncol Res. 1993;5(9):347-56.
Mucins are important in cancer diagnosis and therapy. A better understanding of the characteristics of mucins in normal and malignant tissues could make them more effective clinical targets. Levels of the sialylated carbohydrate mucin antigens CA19-9, DU-PAN-2, SPan-1, and TAG-72 are elevated in sera from patients with pancreatic cancer. In this study we examined normal saliva for the presence of these antigens. TAG-72 reactivity was not detected in the samples examined. SPan-1 expression correlated with the expression of CA19-9 except in Le(a)- individuals. In these individuals CA19-9 was absent; SPan-1 was expressed to varying degrees. Little, if any, reactivity was detected with four monoclonal antibodies directed against the MUC1 mucin peptide. A high-buoyant-density-fraction (1.35 to 1.55 g/mL) of normal saliva, containing most of the sialic acids and O-linked oligosaccharides, was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Western blots showed that CA19-9, DU-PAN-2, and SPan-1 antigens were found on two forms of mucins. DU-PAN-2 reactivity was detected only in the absence of the sulfhydryl reducing agent beta-mercaptoethanol. The two main forms of antigens differed in molecular size (150 kDa and greater than 400 kDa) and buoyant density (1.38 and 1.49 g/mL) and have been reported to differ in amino-acid composition. In colon or pancreas, the CA19-9, DU-PAN-2, and SPan-1 carbohydrate structures have been reported to be present on the MUC1 mucin peptide. Our present results suggest that in saliva, these carbohydrate antigens may be found on mucin peptides other than MUC1.
黏蛋白在癌症诊断和治疗中具有重要意义。更好地了解正常组织和恶性组织中黏蛋白的特征,可使其成为更有效的临床靶点。胰腺癌患者血清中唾液酸化碳水化合物黏蛋白抗原CA19 - 9、DU - PAN - 2、SPan - 1和TAG - 72的水平升高。在本研究中,我们检测了正常唾液中这些抗原的存在情况。在所检测的样本中未检测到TAG - 72反应性。除了Le(a)-个体外,SPan - 1表达与CA19 - 9表达相关。在这些个体中,CA19 - 9缺失;SPan - 1有不同程度的表达。针对MUC1黏蛋白肽的四种单克隆抗体几乎未检测到反应性。通过十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳(SDS - PAGE)分离出正常唾液的高浮力密度级分(1.35至1.55 g/mL),其中包含大部分唾液酸和O - 连接寡糖。蛋白质印迹显示,CA19 - 9、DU - PAN - 2和SPan - 1抗原存在于两种形式的黏蛋白上。仅在不存在巯基还原剂β - 巯基乙醇的情况下检测到DU - PAN - 2反应性。这两种主要形式的抗原在分子大小(150 kDa和大于400 kDa)和浮力密度(1.38和1.49 g/mL)上有所不同,并且据报道在氨基酸组成上也有所不同。在结肠或胰腺中,据报道CA19 - 9、DU - PAN - 2和SPan - 1碳水化合物结构存在于MUC1黏蛋白肽上。我们目前的结果表明,在唾液中,这些碳水化合物抗原可能存在于除MUC1之外的黏蛋白肽上。