异常糖基化CD44和其单抗KMP1与膀胱癌发病机理的关系研究

在前期研究中，我们制备了一种能与膀胱癌特异性结合的单克隆抗体KMP1，体外实验证实它能抑制膀胱癌细胞的生长，已证明它结合的配体是膀胱癌细胞膜上异常糖基化的CD44，并已证明N-乙酰氨基半乳糖转移酶1(GALNT1)参与CD44的异常糖基化。为了进一步了解异常糖基化的CD44和单抗KMP1与膀胱癌发生发展的关系，本研究拟采用活体成像研究KMP1抑制膀胱癌细胞EJ在裸鼠体内成瘤功能；找寻是否有GALNT1以外的其他糖基转移酶参与膀胱癌CD44蛋白的异常糖基化，探寻更多的膀胱癌靶向治疗的位点；探索KMP1能否作为一种特异性瘤标来进行G1级膀胱尿路上皮癌肿瘤干细胞的筛选。为将其开发为一种具有自主知识产权的膀胱癌标记物、肿瘤靶向治疗药物打下基础。

In the previous study, KMP1, a bladder cancer-specific monoclonal antibody, was prepared, and it could inhibit the growth of bladder cancer cells in vitro experiments. Its ligand binding was the bladder cancer cell membrane aberrant glycosylation of CD44. Then,the aberrant glycosylated CD44 may contribute to recur and planting migration of bladder cancer. KMP1 can recognize CD44 of EJ cells specially and inhibits its proliferation and migration in vitro. CD44 silencing can effectively decrease EJ cells immuno- bounding to the monoclonal antibody KMP1 and inhibit the migration and the proliferation of EJ cells in vitro.It was confirmed that N-acetylamino galactosyltransferase 1 (GALNT1) participated the aberrant glycosylation of CD44. GALNT1 knockdown had no remarkable changes in cell migration, Silenced GALNT1 expression significantly inhibits proliferation and tumor growth of bladder cancer in vitro.In order to study the relationship between aberrant glycosylation of CD44 and mAb KMP1 in the development of bladder cancer, optical in vivo imaging will be used to study the the antitumor function of KMP1 to demonstrate whether other glycosyltransferase enzymes involve in the aberrant glycosylation of the CD44 protein, and to explore more targeted therapy sites for human bladder cancer. Moreover, KMP1 will be evaluated whether it can be as a specific tumor, and to screen tumor stem cells that labeled G1 grade bladder cancer. This study can lay the foundation for KMP1 as a bladder cancer marker with independent intellectual property rights and a targeted cancer therapy drug.