Shimizu Momoko, Imai Masaki
First Department of Oral and Maxillofacial Surgery, Osaka Dental University, Hirakata, Osaka 573-1121, Japan.
Biol Pharm Bull. 2008 Dec;31(12):2288-93. doi: 10.1248/bpb.31.2288.
To conserve both form and function in the oral area, effective and selective drugs against oral cancer will be required. We focused on MUC1, a transmembrane glycoprotein, that is considered tumor-associated antigens (TAAs) for cancer therapy. Recently, studies were done to evaluate the patterns of MUC1 expression in oral squamous cell carcinomas (OSCCs) and it was found that higher MUC1 expression correlates with tumor invasion and metastasis. Using oral squamous cell carcinoma cell lines, we demonstrate here that tumor-specific targeting of MUC1 with the specific monoclonal antibody C595 has functional consequences with regard to complement deposition on MUC1-expressing oral cancer cell lines. Anti-MUC1 monoclonal antibody (mAb) also induced complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) to OSCC cells, and these effects were strongly correlated with MUC1 expression. Thus, these results indicate that anti-MUC1 mAb could provide a useful tool against OSCCs, and may provide insight into the development of low side-effect targeting therapy for this malignant disease.
为了在口腔区域保留形态和功能,将需要有效的选择性抗口腔癌药物。我们聚焦于MUC1,一种跨膜糖蛋白,它被认为是癌症治疗中的肿瘤相关抗原(TAAs)。最近,人们开展了研究来评估MUC1在口腔鳞状细胞癌(OSCCs)中的表达模式,发现较高的MUC1表达与肿瘤侵袭和转移相关。利用口腔鳞状细胞癌细胞系,我们在此证明,用特异性单克隆抗体C595对MUC1进行肿瘤特异性靶向,对于补体在表达MUC1的口腔癌细胞系上的沉积具有功能性影响。抗MUC1单克隆抗体(mAb)也诱导了对OSCC细胞的补体依赖性细胞毒性(CDC)和抗体依赖性细胞毒性(ADCC),并且这些效应与MUC1表达密切相关。因此,这些结果表明抗MUC1 mAb可能为对抗OSCCs提供一种有用的工具,并且可能为这种恶性疾病的低副作用靶向治疗的开发提供见解。