Eder I E, Stenzl A, Hobisch A, Cronauer M V, Bartsch G, Klocker H
Department of Urology, University of Innsbruck, Austria.
Br J Cancer. 1997;75(12):1753-60. doi: 10.1038/bjc.1997.299.
We previously detected elevated transforming growth factor beta-1 (TGF-beta1) serum levels in patients with invasive bladder carcinomas. In this study, we therefore investigated whether elevated serum levels correlate with enhanced TGF-beta expression in human bladder tumours. mRNA levels of TGF-beta1, -beta2 and -beta3 were reduced in bladder tumour tissue to 86%, 68% and 56%, respectively, of the levels in normal urothelium. On the other hand, TGF-beta1 protein levels were found to be higher in superficial tumours (Ta-T1) (mean level of 0.153 ng mg(-1)) and in invasive T2/T3 tumours (mean level of 0.104 ng mg(-1)) compared with normal urothelium (mean level of 0.065 ng mg(-1)). Invasive T4 tumours, however, contained only low amounts of TGF-beta1 (mean level of 0.02 ng mg(-1)). Neither in mean nor in individual patients were serum and tissue TGF-beta levels correlated with each other. Cell culture experiments on primary bladder cells revealed a 57% decrease in TGF-beta1 mRNA levels in tumour compared with normal epithelial cells. Tumour epithelial cells contained about two times higher levels of TGF-beta2 and TGF-beta3 mRNA than normal epithelial cells. Fibroblasts expressed about the same amount of TGF-beta1 or TGF-beta2 as epithelial cells. Yet, fibroblasts released only 19% and 13% of the amount secreted by tumour epithelial cells into the supernatant. TGF-beta3, on the other hand, was expressed by fibroblasts with higher levels than by epithelial cells. TGF-beta1 was the predominent isoform in bladder tissue and cells at protein as well as on mRNA levels indicating that TGFs-beta2 and -beta3 are of minor importance in bladder cancer. In summary, there is a lack of correlation between TGF-beta serum levels and TGF-beta expression in tumour tissue in bladder cancer.
我们之前检测到浸润性膀胱癌患者血清中转化生长因子β-1（TGF-β1）水平升高。因此，在本研究中，我们调查了血清水平升高是否与人类膀胱肿瘤中TGF-β表达增强相关。膀胱肿瘤组织中TGF-β1、-β2和-β3的mRNA水平分别降至正常尿路上皮水平的86%、68%和56%。另一方面，与正常尿路上皮（平均水平为0.065 ng mg⁻¹）相比，浅表性肿瘤（Ta-T1）（平均水平为0.153 ng mg⁻¹）和浸润性T2/T3肿瘤（平均水平为0.104 ng mg⁻¹）中TGF-β1蛋白水平更高。然而，浸润性T4肿瘤中仅含有少量的TGF-β1（平均水平为0.02 ng mg⁻¹）。无论是平均水平还是个体患者，血清和组织TGF-β水平均无相关性。对原代膀胱细胞进行的细胞培养实验显示，与正常上皮细胞相比，肿瘤中TGF-β1 mRNA水平降低了57%。肿瘤上皮细胞中TGF-β2和TGF-β3 mRNA水平比正常上皮细胞高约两倍。成纤维细胞表达的TGF-β1或TGF-β2与上皮细胞大致相同。然而，成纤维细胞释放到上清液中的量仅为肿瘤上皮细胞分泌量的19%和13%。另一方面，成纤维细胞表达的TGF-β3水平高于上皮细胞。TGF-β1在膀胱组织和细胞的蛋白及mRNA水平上都是主要的异构体，表明TGF-β2和-β3在膀胱癌中的重要性较小。总之，膀胱癌患者血清TGF-β水平与肿瘤组织中TGF-β表达之间缺乏相关性。
