Nakai T, Endo K, Hosono M, Saga T, Watanabe Y, Sakahara H, Imai K, Yachi A, Kiyozuka Y, Ishiwata I
Department of Nuclear Medicine, Kyoto University School of Medicine, Japan.
Int J Cancer. 1991 May 30;48(3):463-7. doi: 10.1002/ijc.2910480326.
CA125 is a high-molecular weight glycoprotein expressed on most serous-type ovarian cancer and some lung adenocarcinoma tissues. The effects of various drugs on the release of CA125 antigen into culture medium and on monoclonal antibody (MAb) binding to cancer cells were studied using 8 human cancer cell lines, all of which expressed CA125 on their cell surfaces. The effect of dexamethasone was seen at as low a concentration as 10(-9) M dexamethasone, and the release of CA125 and the binding of radiolabelled anti-CA125 antibody were completely inhibited after exposure to 10(-7) M dexamethasone. The number of antibody binding sites markedly decreased. In contrast, sodium butyrate increased CA125 expression. These findings were clearly detected in only 3 cancer cell lines and a significant effect was not seen in the 5 other cancer cell lines. Interferon-gamma, examined in 3 cell lines, suppressed in a dose-dependent manner in 2 CA125 expression cell lines, but enhanced it in one line. No apparent effects were seen after exposure to tissue necrosis factor or interleukin-2. These results suggest that drugs may regulate the CA125 antigen expression in some, but not all, cancer cells and may affect the biodistribution of radiolabelled MAbs.
CA125是一种高分子量糖蛋白,在大多数浆液性卵巢癌和一些肺腺癌组织中表达。使用8种人类癌细胞系研究了各种药物对CA125抗原释放到培养基中以及对单克隆抗体(MAb)与癌细胞结合的影响,所有这些细胞系在其细胞表面均表达CA125。地塞米松在低至10^(-9) M的浓度下就可见其作用,在暴露于10^(-7) M地塞米松后,CA125的释放以及放射性标记的抗CA125抗体的结合被完全抑制。抗体结合位点的数量明显减少。相反,丁酸钠增加了CA125的表达。这些发现仅在3种癌细胞系中明显检测到,而在其他5种癌细胞系中未观察到显著作用。在3种细胞系中检测的干扰素-γ,在2种表达CA125的细胞系中以剂量依赖性方式抑制了CA125的表达,但在一种细胞系中增强了其表达。暴露于组织坏死因子或白细胞介素-2后未观察到明显作用。这些结果表明,药物可能在某些但并非所有癌细胞中调节CA125抗原的表达,并可能影响放射性标记单克隆抗体的生物分布。