Interleukin 1β Enhances Invasive Ability of Gastric Carcinoma through Nuclear Factor-κB Activation

Naoki Yamanaka, Takashi Morisaki, Hiroshi Nakashima, Akira Tasaki, Makoto Kubo, Hirotaka Kuga, Chihiro Nakahara, Katsuya Nakamura, Hirokazu Noshiro, Takashi Yao, Masazumi Tsuneyoshi, Masao Tanaka, Mitsuo Katano

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36 Citations (Scopus)

Abstract

Purpose: We examined the role of interleukin (IL)-1β in activation of nuclear factor κB (NF-κB) and the biological function of activated NF-κB in gastric carcinoma cells. Experimental Design: Human gastric carcinoma cell line GCTM-1 was used to examine NF-κB activation by immunostaining and electrophoretic mobility shift assay. Matrix metalloproteinase (MMP)-9 expression, which plays an important role in tumor invasion, was assessed by semiquantitative reverse transcription-PCR, Western blotting, and immunostaining. The invasive ability of GCTM-1 cells was measured by Matrigel invasion assay. In vivo expression of IL-1β and MMP-9 and activation of NF-κB in 10 surgically resected gastric carcinoma specimens were examined immunohistochemically. Results: IL-1β enhanced NF-κB activation, MMP-9 expression, and the invasive ability of GCTM-1. A NF-κB inhibitor, pyrrolidine dithiocarbamate, suppressed both MMP-9 expression and invasiveness of IL-1κ-treated GCTM-1 cells. IL-1β did not increase the invasive ability of GCTM-1 cells transfected with MMP-9 antisense oligonucleotide. Concomitant expression of IL-1β and nuclear NF-κB was observed in 3 of 10 gastric carcinoma specimens. Cells producing IL-1β were tumor-infiltrating macrophages in two specimens and gastric carcinoma cells in one specimen. Conclusions: One of the molecules that may play a role in NF-κB activation in some gastric carcinomas is IL-1β. The present results suggest that IL-1β increases the invasive ability of carcinoma cells through activation of NF-βB and the resulting MMP-9 expression.

Original languageEnglish
Pages (from-to)1853-1859
Number of pages7
JournalClinical Cancer Research
Volume10
Issue number5
DOIs
Publication statusPublished - Mar 1 2004

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Yamanaka, N., Morisaki, T., Nakashima, H., Tasaki, A., Kubo, M., Kuga, H., Nakahara, C., Nakamura, K., Noshiro, H., Yao, T., Tsuneyoshi, M., Tanaka, M., & Katano, M. (2004). Interleukin 1β Enhances Invasive Ability of Gastric Carcinoma through Nuclear Factor-κB Activation. Clinical Cancer Research, 10(5), 1853-1859. https://doi.org/10.1158/1078-0432.CCR-03-0300