哺乳动物细胞内的某些蛋白质或脂类可以被糖基化修饰,而糖链末端往往存在唾液酸化的现象,催化添加唾液酸的酶为糖基转移酶(sialyltransferase,ST),而去除唾液酸的为唾液酸酶(sialidase,sA或称为neuraminidase,NELl).本实验检测了人膀胱正常上皮细胞HCV29、非浸润性膀胱癌细胞KK47和浸润性膀胱癌细胞YTS-1中唾液酸的表达,发现恶性肿瘤细胞中唾液酸的含量高于正常细胞;进一步分析唾液酸酶和唾液酸转移酶的表达,发现唾液酸酶Neul在正常细胞中表达最高,在良性肿瘤细胞中次之,在恶性肿瘤细胞中表达最低,推测在膀胱癌中Neul对唾液酸的异常表达起着主要作用.同时,膀胱癌细胞中Toll样受体1,2,3,4(toll.1ikereceptors,TLRs)表达趋势也与Neul一致.利用TGF.B处理HCV29,使之发生上皮间质转化(epithelial.mesenchymaltransition,EMT),细胞中Neul和TLR3表达明显减少;将Neul基因沉默后,TLR3表达也明显减少.此外,在YTS.1细胞中过表达Neul,TLR3表达增高且激活了下游NF.KB通路.这一结果说明膀胱癌中Neul与TLR3的表达有着密切的关系,这为膀胱癌的分子机理研究提供了工作基础.
Sialyltransferase (ST) and sialidase (SA) are the main enzymes responsible for the addition or removal of sialic acids to the terminal of glycan on glycoprotein or glycolipids. In our study, the expression of sialic acids, sialidases and sialyltransferases in normal bladder epithelial cell line HCV29, and two bladder cancer cell lines KK47 and YTS-1 were detected. Our results showed YTS-1 cells, the highly invasive cell line, expressed higher level of sialic acids than other two cell lines. However, the level of Neul in YTS-1 cells was the lowest among all the cell lines. The expression of Toll like receptors TLR1,2,3,4 was consistent with neul expression in these three cell lines. When normal bladder cell HCV29 underwent TGF-[3 induced epithelial to mesenchymal transition (EMT) process, expression of Neul and TLR3 were significantly decreased. When Neul expression was inhibited in HCV29 cell line, the level of TLR3 was also reduced. Overexpression of Neul in YTS-lcells resulted in TLR3 increase accompanied with the activation of NF-KB signaling pathway. Our results indicated that Neul shared closed relationship with the expression of TLRs in bladder cancer cells, which may potentially provide therapeutic candidates in treating bladder cancer.