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

• Published in: Clinical cancer research 2004-03, Vol.10 (5), p.1853-1859
• Main Authors: YAMANAKA, Naoki, MORISAKI, Takashi, TSUNEYOSHI, Masazumi, TANAKA, Masao, KATANO, Mitsuo, NAKASHIMA, Hiroshi, TASAKI, Akira, KUBO, Makoto, KUGA, Hirotaka, NAKAHARA, Chihiro, NAKAMURA, Katsuya, NOSHIRO, Hirokazu, YAO, Takashi
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Medical sciences; Pharmacology. Drug treatments; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-03-0300

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-1β-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-κB and the resulting MMP-9 expression.