转化生长因子-β1对人肝内胆管癌细胞生长的影响。
Effect of transforming growth factor-beta1 on human intrahepatic cholangiocarcinoma cell growth.
作者信息
Shimizu Tetsuya, Yokomuro Shigeki, Mizuguchi Yoshiaki, Kawahigashi Yutaka, Arima Yasuo, Taniai Nobuhiko, Mamada Yasuhiro, Yoshida Hiroshi, Akimaru Koho, Tajiri Takashi
机构信息
Surgery for Organ Function and Biological Regulation, Graduate school of medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
出版信息
World J Gastroenterol. 2006 Oct 21;12(39):6316-24. doi: 10.3748/wjg.v12.i39.6316.
AIM
To elucidate the biological effects of transforming growth factor-beta1 (TGF-beta1) on intrahepatic cholan-giocarcinoma (ICC).
METHODS
We investigated the effects of TGF-beta1 on human ICC cell lines (HuCCT1, MEC, and HuH-28) by monitoring the influence of TGF-beta1 on tumor growth and interleukin-6 (IL-6) expression in ICC cells.
RESULTS
All three human ICC cell lines produced TGF-beta1 and demonstrated accelerated growth in the presence of TGF-beta1 with no apoptotic effect. Studies on HuCCT1 revealed a TGF-beta1-induced stimulation of the expression of TGF-beta1, as well as a decrease in TGF-beta1 mRNA expression induced by neutralizing anti-TGF-beta1 antibody. These results indicate that TGF-beta1 stimulates the production and function of TGF-beta1 in an autocrine fashion. Further, IL-6 secretion was observed in all three cell lines and exhibited an inhibitory response to neutralizing anti-TGF-beta1 antibody. Experiments using HuCCT1 revealed a TGF-beta1-induced acceleration of IL-6 protein expression and mRNA levels. These findings demonstrate a functional interaction between TGF-beta1 and IL-6. All three cell lines proliferated in the presence of IL-6. In contrast, TGF-beta1 induced no growth effect in HuCCT1 in the presence of small interfering RNA against a specific cell surface receptor of IL-6 and signal transducer and activator of transcription-3.
CONCLUSION
ICC cells produce TGF-beta1 and confer a TGF-beta1-induced growth effect in an autocrine fashion. TGF-beta1 activates IL-6 production, and the functional interaction between TGF-beta1 and IL-6 contributes to ICC cell growth by TGF-beta1.
目的
阐明转化生长因子-β1（TGF-β1）对肝内胆管癌（ICC）的生物学作用。
方法
通过监测TGF-β1对ICC细胞肿瘤生长和白细胞介素-6（IL-6）表达的影响，研究TGF-β1对人ICC细胞系（HuCCT1、MEC和HuH-28）的作用。
结果
所有三种人ICC细胞系均产生TGF-β1，并且在存在TGF-β1的情况下显示出加速生长，无凋亡效应。对HuCCT1的研究显示，TGF-β1诱导TGF-β1表达的刺激，以及中和抗TGF-β1抗体诱导的TGF-β1 mRNA表达的降低。这些结果表明，TGF-β1以自分泌方式刺激TGF-β1的产生和功能。此外，在所有三种细胞系中均观察到IL-6分泌，并且对中和抗TGF-β1抗体表现出抑制反应。使用HuCCT1的实验显示，TGF-β1诱导IL-6蛋白表达和mRNA水平加速。这些发现证明了TGF-β1与IL-6之间的功能相互作用。所有三种细胞系在IL-6存在下均增殖。相反，在存在针对IL-6特异性细胞表面受体以及信号转导和转录激活因子-3的小干扰RNA的情况下，TGF-β1对HuCCT1未诱导生长效应。
结论
ICC细胞产生TGF-β1，并以自分泌方式赋予TGF-β1诱导的生长效应。TGF-β1激活IL-6的产生，并且TGF-β1与IL-6之间的功能相互作用通过TGF-β1促进ICC细胞生长。
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