PMID- 19218340
OWN - NLM
STAT- MEDLINE
DCOM- 20090323
LR  - 20211020
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 174
IP  - 3
DP  - 2009 Mar
TI  - Cyclooxygenase-2 is involved in the up-regulation of matrix metalloproteinase-9 
      in cholangiocarcinoma induced by tumor necrosis factor-alpha.
PG  - 829-41
LID - 10.2353/ajpath.2009.080012 [doi]
AB  - Matrix metalloproteinase-9 (MMP-9) is an important enzyme in tumor invasion and 
      metastasis in malignant tumors, including cholangiocarcinoma (CC). Tumor necrosis 
      factor-alpha (TNF-alpha), a proinflammatory cytokine, was recently reported to 
      induce the up-regulation of MMP-9 in cultured CC cells. We examined whether 
      cyclooxygenase-2 (COX-2) and prostaglandin-E2 (PGE2), another endogenous tumor 
      promoter, are involved in the up-regulation of MMP-9 in CC using CC tissue 
      specimens and a CC cell line, HuCCT-1. MMP-9 and COX-2 were immunohistochemically 
      expressed in 58% and 89% of 110 CC cases, respectively; the expression of MMP-9 
      and COX-2 was correlated (r = 0.32, P = 0.00072). Using zymography, latent MMP-9 
      was detectable in all cases and active MMP-9 was detected in 24% of cases of the 
      CC specimens. The TNF-alpha/TNF-receptor 1 (TNF-R1) interaction induced MMP-9 
      production and activation, as well as COX-2 overexpression and PGE2 production, 
      and increased the migration of CC cells. MMP-9 up-regulation was inhibited by COX 
      inhibitors, antagonists of EP2/4 (receptors of PGE2), and COX-1 and COX-2 siRNAs. 
      Inhibitors of both MMP-9 and MMP-9 siRNA treatment abrogated the increase in the 
      migration of CC cells induced by TNF-alpha. In conclusion, we propose a novel 
      signaling pathway of MMP-9 up-regulation in CC cells such that TNF-alpha induces 
      the activation of COX-2 and PGE2 via TNF-R1 followed by the up-regulation of 
      MMP-9 via the PGE2 (EP2/4) receptor.
FAU - Itatsu, Keita
AU  - Itatsu K
AD  - Department of Human Pathology, Kanazawa University Graduate School of Medicine, 
      Kanazawa 920-8640, Japan.
FAU - Sasaki, Motoko
AU  - Sasaki M
FAU - Yamaguchi, Junpei
AU  - Yamaguchi J
FAU - Ohira, Shusaku
AU  - Ohira S
FAU - Ishikawa, Akira
AU  - Ishikawa A
FAU - Ikeda, Hiroko
AU  - Ikeda H
FAU - Sato, Yasunori
AU  - Sato Y
FAU - Harada, Kenichi
AU  - Harada K
FAU - Zen, Yoh
AU  - Zen Y
FAU - Sato, Hiroshi
AU  - Sato H
FAU - Ohta, Tetsuo
AU  - Ohta T
FAU - Nagino, Masato
AU  - Nagino M
FAU - Nimura, Yuji
AU  - Nimura Y
FAU - Nakanuma, Yasuni
AU  - Nakanuma Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090213
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Receptors, Prostaglandin E)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Bile Duct Neoplasms/chemically induced/*enzymology/genetics
MH  - Bile Ducts, Intrahepatic/enzymology/pathology
MH  - Cholangiocarcinoma/chemically induced/*enzymology/genetics/pathology
MH  - Cyclooxygenase 2/*genetics
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Lymphatic Metastasis
MH  - Male
MH  - Matrix Metalloproteinase 9/*genetics
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Promoter Regions, Genetic
MH  - Receptors, Prostaglandin E/physiology
MH  - Tumor Necrosis Factor-alpha/*toxicity
MH  - Up-Regulation
PMC - PMC2665744
EDAT- 2009/02/17 09:00
MHDA- 2009/03/24 09:00
PMCR- 2009/09/01
CRDT- 2009/02/17 09:00
PHST- 2009/02/17 09:00 [entrez]
PHST- 2009/02/17 09:00 [pubmed]
PHST- 2009/03/24 09:00 [medline]
PHST- 2009/09/01 00:00 [pmc-release]
AID - S0002-9440(10)60943-1 [pii]
AID - 10.2353/ajpath.2009.080012 [doi]
PST - ppublish
SO  - Am J Pathol. 2009 Mar;174(3):829-41. doi: 10.2353/ajpath.2009.080012. Epub 2009 
      Feb 13.