Doi Mihoko, Yokoyama Akihito, Kondo Keiichi, Ohnishi Hiroshi, Ishikawa Nobuhisa, Hattori Noboru, Kohno Nobuoki
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Cancer Sci. 2006 May;97(5):420-9. doi: 10.1111/j.1349-7006.2006.00183.x.
Human polymorphic epithelial mucin (MUC1) is a heavily glycosylated large protein that is frequently overexpressed on the surface of many human adenocarcinomas. Studies using monoclonal antibodies (mAb) identified MUC1 as a tumor-associated antigen that has been intensely studied as a target for cancer immunotherapy. We previously identified a mouse IgG(1) mAb that recognizes a sialylated sugar chain, designated as KL-6, classified in 'Cluster 9 (MUC1)'. Using the anti-KL-6 mAb, we investigated antitumor effects of anti-MUC1 mAb on breast cancer cell lines expressing MUC1 abundantly. We showed that anti-KL-6 mAb induced capping of MUC1 and facilitated E-cadherin-mediated cell-cell interaction in the breast cancer cell lines YMB-S and ZR-75-1S, which proliferate in suspension culture without aggregation. Moreover, anti-KL-6 mAb enhanced the cytotoxic activity of lymphokine-activated killer cells. These results indicate that the capping of MUC1 restores cell surface proteins, such as adhesion molecules and tumor antigens, to work in cell-cell interactions, leading to inhibition of tumor proliferation due to cell-cell adhesion and increased accessibility to effector cells that are needed to kill tumor cells.
人多形性上皮粘蛋白（MUC1）是一种高度糖基化的大蛋白，在许多人腺癌表面经常过度表达。使用单克隆抗体（mAb）的研究将MUC1鉴定为一种肿瘤相关抗原，作为癌症免疫治疗的靶点已受到深入研究。我们之前鉴定出一种识别唾液酸化糖链的小鼠IgG(1) mAb，命名为KL-6，归类于“第9簇（MUC1）”。使用抗KL-6 mAb，我们研究了抗MUC1 mAb对大量表达MUC1的乳腺癌细胞系的抗肿瘤作用。我们发现抗KL-6 mAb在乳腺癌细胞系YMB-S和ZR-75-1S中诱导了MUC1的帽化，并促进了E-钙粘蛋白介导的细胞间相互作用，这两种细胞系在悬浮培养中增殖而不聚集。此外，抗KL-6 mAb增强了淋巴因子激活的杀伤细胞的细胞毒活性。这些结果表明，MUC1的帽化恢复了细胞表面蛋白，如粘附分子和肿瘤抗原，以在细胞间相互作用中发挥作用，导致由于细胞间粘附而抑制肿瘤增殖，并增加对杀死肿瘤细胞所需效应细胞的可及性。
