Interleukin 1beta enhances invasive ability of gastric carcinoma through nuclear factor-kappaB activation.
OBJECTIVE
We examined the role of interleukin (IL)-1beta in activation of nuclear factor kappaB (NF-kappaB) and the biological function of activated NF-kappaB in gastric carcinoma cells.


METHODS
Human gastric carcinoma cell line GCTM-1 was used to examine NF-kappaB 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-1beta and MMP-9 and activation of NF-kappaB in 10 surgically resected gastric carcinoma specimens were examined immunohistochemically.


RESULTS
IL-1beta enhanced NF-kappaB activation, MMP-9 expression, and the invasive ability of GCTM-1. A NF-kappaB inhibitor, pyrrolidine dithiocarbamate, suppressed both MMP-9 expression and invasiveness of IL-1beta-treated GCTM-1 cells. IL-1beta did not increase the invasive ability of GCTM-1 cells transfected with MMP-9 antisense oligonucleotide. Concomitant expression of IL-1beta and nuclear NF-kappaB was observed in 3 of 10 gastric carcinoma specimens. Cells producing IL-1beta 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-kappaB activation in some gastric carcinomas is IL-1beta. The present results suggest that IL-1beta increases the invasive ability of carcinoma cells through activation of NF-kappaB and the resulting MMP-9 expression.
Yamanaka
Naoki
N
Departments of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Morisaki
Takashi
T
Nakashima
Hiroshi
H
Tasaki
Akira
A
Kubo
Makoto
M
Kuga
Hirotaka
H
Nakahara
Chihiro
C
Nakamura
Katsuya
K
Noshiro
Hirokazu
H
Yao
Takashi
T
Tsuneyoshi
Masazumi
M
Tanaka
Masao
M
Katano
Mitsuo
M
D001483:Base Sequence; D045744:Cell Line, Tumor; D003094:Collagen; D004338:Drug Combinations; D006801:Humans; D007375:Interleukin-1 / Q000633:toxicity*; D007797:Laminin; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011509:Proteoglycans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000473:pathology*
D004338:Drug Combinations; D007375:Interleukin-1; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D020780:Matrix Metalloproteinase 9