CD70 (TNFSF7) is expressed at high prevalence in renal cell carcinomas and is rapidly internalised on antibody binding
CD70 (TNFSF7) is expressed at high prevalence in renal cell carcinomas and is rapidly internalised on antibody binding
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DOI：
10.1038/sj.bjc.6603222
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发表时间：
2006-08-07
影响因子：
8.8
通讯作者：
Harris, A. L.
中科院分区：
文献类型：
--
作者：
Adam, P. J.;Terrett, J. A.;Harris, A. L.
为了确定肾癌的潜在标志物，用蛋白质组学方法对肾细胞癌(RCC)来源细胞系的质膜蛋白含量进行了注释。在A498和786-O细胞中发现的一种不寻常的蛋白质是CD70(TNFSF7)，它是一种II型跨膜受体，通常在B、T和NK细胞的亚群上表达，在免疫细胞激活中发挥协同刺激作用。CD70在多种癌组织中表达的免疫组织化学分析显示，CD70在肾癌组织中呈强阳性表达。11例肾透明细胞癌转移组织中8例CD70表达阳性。免疫细胞化学分析表明，抗CD70抗体与内源性表达在A498和786-O细胞表面的CD70结合，导致抗体-受体复合体迅速内化。在加入A498细胞之前，内化的抗CD70抗体与皂苷偶联的二抗共孵育后，细胞杀伤率为50%。这些数据表明，CD70是一种潜在的靶抗原，可用于治疗肾癌的毒素偶联治疗性抗体。
In order to identify potential markers of renal cancer, the plasma membrane protein content of renal cell carcinoma (RCC)-derived cell lines was annotated using a proteomics process. One unusual protein identified at high levels in A498 and 786-O cells was CD70 (TNFSF7), a type II transmembrane receptor normally expressed on a subset of B, T and NK cells, where it plays a costimulatory role in immune cell activation. Immunohistochemical analysis of CD70 expression in multiple carcinoma types demonstrated strong CD70 staining in RCC tissues. Metastatic tissues from eight of 11 patients with clear cell RCC were positive for CD70 expression. Immunocytochemical analysis demonstrated that binding of an anti-CD70 antibody to CD70 endogenously expressed on the surface of A498 and 786-O cell lines resulted in the rapid internalisation of the antibody-receptor complex. Coincubation of the internalising anti-CD70 antibody with a saporin-conjugated secondary antibody before addition to A498 cells resulted in 50% cell killing. These data indicate that CD70 represents a potential target antigen for toxin-conjugated therapeutic antibody treatment of RCC.