Effect of transforming growth factor-&beta;1 on human intrahepatic cholangiocarcinoma cell growth

doi:10.3748/wjg.v12.i39.6316

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Oct 21, 2006 (publication date) through Nov 5, 2024

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Research

World J Gastroenterol. Oct 21, 2006; 12(39): 6316-6324
Published online Oct 21, 2006. doi: 10.3748/wjg.v12.i39.6316

Effect of transforming growth factor-β1 on human intrahepatic cholangiocarcinoma cell growth

Tetsuya Shimizu, Shigeki Yokomuro, Yoshiaki Mizuguchi, Yutaka Kawahigashi, Yasuo Arima, Nobuhiko Taniai, Yasuhiro Mamada, Hiroshi Yoshida, Koho Akimaru, Takashi Tajiri

Tetsuya Shimizu, Shigeki Yokomuro, Yoshiaki Mizuguchi, Yutaka Kawahigashi, Yasuo Arima, Nobuhiko Taniai, Yasuhiro Mamada, Hiroshi Yoshida, Koho Akimaru, Takashi Tajiri, Surgery for Organ Function and Biological Regulation, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan

Supported by the Ministry of Education, Science, Sports, and Culture of Japan, through a Grant-in-Aid for Scientific Research (C)

Correspondence to: Dr. Tetsuya Shimizu, Surgery for Organ Function and Biological Regulation, Graduate school of medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan. tetsuya@nms.ac.jp

Telephone: +81-3-58146239 Fax: +81-3-56850989

Received: May 15, 2006
Revised: May 28, 2006
Accepted: July 18, 2006
Published online: October 21, 2006

Abstract

AIM: To elucidate the biological effects of transforming growth factor-β1 (TGF-β1) on intrahepatic cholan-giocarcinoma (ICC).

METHODS: We investigated the effects of TGF-β1 on human ICC cell lines (HuCCT1, MEC, and HuH-28) by monitoring the influence of TGF-β1 on tumor growth and interleukin-6 (IL-6) expression in ICC cells.

RESULTS: All three human ICC cell lines produced TGF-β1 and demonstrated accelerated growth in the presence of TGF-β1 with no apoptotic effect. Studies on HuCCT1 revealed a TGF-β1-induced stimulation of the expression of TGF-β1, as well as a decrease in TGF-β1 mRNA expression induced by neutralizing anti-TGF-β1 antibody. These results indicate that TGF-β1 stimulates the production and function of TGF-β1 in an autocrine fashion. Further, IL-6 secretion was observed in all three cell lines and exhibited an inhibitory response to neutralizing anti-TGF-β1 antibody. Experiments using HuCCT1 revealed a TGF-β1-induced acceleration of IL-6 protein expression and mRNA levels. These findings demonstrate a functional interaction between TGF-β1 and IL-6. All three cell lines proliferated in the presence of IL-6. In contrast, TGF-β1 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-β1 and confer a TGF-β1-induced growth effect in an autocrine fashion. TGF-β1 activates IL-6 production, and the functional interaction between TGF-β1 and IL-6 contributes to ICC cell growth by TGF-β1.

Keywords: Transforming growth factor-β1; Interleukin-6; Intrahepatic cholangiocarcinoma