TLR2信号通路促进VEGF和TGF-β1分泌参与膀胱癌癌细胞免疫逃逸

TLR2 signaling pathways favor immune escape of bladder cancer cells by promoting VEGF and TGF-β1 secretion

目的研究膀胱癌癌细胞株T24的VEGF、TGF-β1分泌与TLR2信号通路的关系。方法采用实时荧光定量RT-PCR检测膀胱癌细胞株T24的TLR2表达情况;使用实时荧光定量RT-PCR和ELISA检测经TLR2激活物肽聚糖处理前后癌细胞VEGF及TGF-β1 mRNA的水平及蛋白质分泌状况;使用实时荧光定量RT-PCR和ELISA检测采取抗TLR2抗体封闭后再用肽聚糖处理前后肿瘤细胞VEGF和TGF-β1 mRNA的水平及蛋白质分泌状况。结果膀胱癌细胞株T24膜上有TLR2表达;经TLR2激活物肽聚糖处理后癌细胞VEGF及TGF-β1 mRNA的水平显著增高,在细胞培养上清液中蛋白质分泌水平同样显著增高;在采用抗TLR2抗体封闭TLR2后,肽聚糖的刺激不会引起癌细胞VEGF和TGF-β1 mRNA的水平及蛋白质分泌水平的增高。结论 TLR2信号通路促进VEGF和TGF-β1分泌参与膀胱癌细胞免疫逃逸,这对预防、诊断和治疗膀胱癌可能会发挥重要作用。

This study performed to investigate the relationship between TLR2 signaling pathways and thesecretion of VEGF and TGF-β1 in urinary bladder neoplasms cells. Real-time fluorescent quantitative PCR wasused to detect TLR2 expression in T24 urinary bladder neoplasms cells; Real-time fluorescent quantitative PCR andELISA were used to detect the m RNA and protein levels of VEGF and TGF-β1 in the tumor cells processed byTLR2 activators peptidoglycan or not. Furthermore, the m RNA and protein levels of VEGF and TGF-β1 weredetected in anti-TLR2 antibody-blocked tumor cells, which were processed by TLR2 activators peptidoglycan ornot. Data showed that TLR2 could be detected on surface of T24 urinary bladder neoplasms cells; the m RNA andprotein levels of VEGF and TGF-β1 increased significantly in the cell culture supernatant of TLR2 activatorpeptidoglycan processed tumor cells, while blockage of anti-TLR2 antibody could reverse the increase. We concludedthat TLR2 signaling pathways participate in the immune escape by promoting the secretion of VEGF and TGF-β1 inurinary bladder neoplasms cells, and may play an important role in the prevention, diagnose and therapy of urinarybladder neoplasms.