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Stimulation of Peritoneal Mesothelial Cells to Secrete Matrix Metalloproteinase-9 (MMP-9) by TNF-α: A Role in the Invasion of Gastric Carcinoma Cells

It has recently been recognized that inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), upregulate the secretion of matrix metalloproteinase-9 (MMP-9) from cancer cells and thereby promote peritoneal dissemination. In this study, we found that TNF-α also stimulated peritoneal mesotheli...

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Autores principales: Oku, Teruaki, Shimada, Kentaro, Kenmotsu, Hiroki, Ando, Yusuke, Kurisaka, Chisato, Sano, Rikio, Tsuiji, Makoto, Hasegawa, Shinya, Fukui, Tetsuya, Tsuji, Tsutomu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321609/
https://www.ncbi.nlm.nih.gov/pubmed/30544870
http://dx.doi.org/10.3390/ijms19123961
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author Oku, Teruaki
Shimada, Kentaro
Kenmotsu, Hiroki
Ando, Yusuke
Kurisaka, Chisato
Sano, Rikio
Tsuiji, Makoto
Hasegawa, Shinya
Fukui, Tetsuya
Tsuji, Tsutomu
author_facet Oku, Teruaki
Shimada, Kentaro
Kenmotsu, Hiroki
Ando, Yusuke
Kurisaka, Chisato
Sano, Rikio
Tsuiji, Makoto
Hasegawa, Shinya
Fukui, Tetsuya
Tsuji, Tsutomu
author_sort Oku, Teruaki
collection PubMed
description It has recently been recognized that inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), upregulate the secretion of matrix metalloproteinase-9 (MMP-9) from cancer cells and thereby promote peritoneal dissemination. In this study, we found that TNF-α also stimulated peritoneal mesothelial cells to secrete MMP-9 as assessed by zymography. MMP-9 gene expression in mesothelial cells induced by TNF-α was confirmed by quantitative RT-PCR analysis. We then utilized the reconstituted artificial mesothelium, which was composed of a monolayer of mesothelial cells cultured on a Matrigel layer in a Boyden chamber system, to examine the effects of TNF-α on carcinoma cell invasion. The transmigration of MKN1 human gastric carcinoma cells through the reconstituted mesothelium was promoted by TNF-α in a dose-dependent manner. The increased MKN1 cell migration was partially inhibited by the anti-α3 integrin antibody, indicating that the invasion process involves an integrin-dependent mechanism. Finally, we observed that the invasion of MMP-9-knockdown MKN1 cells into Matrigel membranes was potentiated by the exogenous addition of purified proMMP-9. These results suggest that TNF-α-induced MMP-9 secretion from mesothelial cells plays an important role in the metastatic dissemination of gastric cancer.
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spelling pubmed-63216092019-01-07 Stimulation of Peritoneal Mesothelial Cells to Secrete Matrix Metalloproteinase-9 (MMP-9) by TNF-α: A Role in the Invasion of Gastric Carcinoma Cells Oku, Teruaki Shimada, Kentaro Kenmotsu, Hiroki Ando, Yusuke Kurisaka, Chisato Sano, Rikio Tsuiji, Makoto Hasegawa, Shinya Fukui, Tetsuya Tsuji, Tsutomu Int J Mol Sci Article It has recently been recognized that inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), upregulate the secretion of matrix metalloproteinase-9 (MMP-9) from cancer cells and thereby promote peritoneal dissemination. In this study, we found that TNF-α also stimulated peritoneal mesothelial cells to secrete MMP-9 as assessed by zymography. MMP-9 gene expression in mesothelial cells induced by TNF-α was confirmed by quantitative RT-PCR analysis. We then utilized the reconstituted artificial mesothelium, which was composed of a monolayer of mesothelial cells cultured on a Matrigel layer in a Boyden chamber system, to examine the effects of TNF-α on carcinoma cell invasion. The transmigration of MKN1 human gastric carcinoma cells through the reconstituted mesothelium was promoted by TNF-α in a dose-dependent manner. The increased MKN1 cell migration was partially inhibited by the anti-α3 integrin antibody, indicating that the invasion process involves an integrin-dependent mechanism. Finally, we observed that the invasion of MMP-9-knockdown MKN1 cells into Matrigel membranes was potentiated by the exogenous addition of purified proMMP-9. These results suggest that TNF-α-induced MMP-9 secretion from mesothelial cells plays an important role in the metastatic dissemination of gastric cancer. MDPI 2018-12-09 /pmc/articles/PMC6321609/ /pubmed/30544870 http://dx.doi.org/10.3390/ijms19123961 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Oku, Teruaki
Shimada, Kentaro
Kenmotsu, Hiroki
Ando, Yusuke
Kurisaka, Chisato
Sano, Rikio
Tsuiji, Makoto
Hasegawa, Shinya
Fukui, Tetsuya
Tsuji, Tsutomu
Stimulation of Peritoneal Mesothelial Cells to Secrete Matrix Metalloproteinase-9 (MMP-9) by TNF-α: A Role in the Invasion of Gastric Carcinoma Cells
title Stimulation of Peritoneal Mesothelial Cells to Secrete Matrix Metalloproteinase-9 (MMP-9) by TNF-α: A Role in the Invasion of Gastric Carcinoma Cells
title_full Stimulation of Peritoneal Mesothelial Cells to Secrete Matrix Metalloproteinase-9 (MMP-9) by TNF-α: A Role in the Invasion of Gastric Carcinoma Cells
title_fullStr Stimulation of Peritoneal Mesothelial Cells to Secrete Matrix Metalloproteinase-9 (MMP-9) by TNF-α: A Role in the Invasion of Gastric Carcinoma Cells
title_full_unstemmed Stimulation of Peritoneal Mesothelial Cells to Secrete Matrix Metalloproteinase-9 (MMP-9) by TNF-α: A Role in the Invasion of Gastric Carcinoma Cells
title_short Stimulation of Peritoneal Mesothelial Cells to Secrete Matrix Metalloproteinase-9 (MMP-9) by TNF-α: A Role in the Invasion of Gastric Carcinoma Cells
title_sort stimulation of peritoneal mesothelial cells to secrete matrix metalloproteinase-9 (mmp-9) by tnf-α: a role in the invasion of gastric carcinoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321609/
https://www.ncbi.nlm.nih.gov/pubmed/30544870
http://dx.doi.org/10.3390/ijms19123961
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