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 stim...
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2018-12-01
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author | Teruaki Oku Kentaro Shimada Hiroki Kenmotsu Yusuke Ando Chisato Kurisaka Rikio Sano Makoto Tsuiji Shinya Hasegawa Tetsuya Fukui Tsutomu Tsuji |
author_facet | Teruaki Oku Kentaro Shimada Hiroki Kenmotsu Yusuke Ando Chisato Kurisaka Rikio Sano Makoto Tsuiji Shinya Hasegawa Tetsuya Fukui Tsutomu Tsuji |
author_sort | Teruaki Oku |
collection | DOAJ |
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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issn | 1422-0067 |
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spelling | doaj.art-a78cb114b2b14f3fa4a82ae9c44a9e6b2022-12-22T03:12:50ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-12-011912396110.3390/ijms19123961ijms19123961Stimulation of Peritoneal Mesothelial Cells to Secrete Matrix Metalloproteinase-9 (MMP-9) by TNF-α: A Role in the Invasion of Gastric Carcinoma CellsTeruaki Oku0Kentaro Shimada1Hiroki Kenmotsu2Yusuke Ando3Chisato Kurisaka4Rikio Sano5Makoto Tsuiji6Shinya Hasegawa7Tetsuya Fukui8Tsutomu Tsuji9Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, JapanDepartment of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, JapanDepartment of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, JapanDepartment of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, JapanDepartment of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, JapanDepartment of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, JapanDepartment of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, JapanDepartment of Health Chemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, JapanDepartment of Health Chemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, JapanDepartment of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, JapanIt 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.https://www.mdpi.com/1422-0067/19/12/3961TNF-αmatrix metalloproteinaseperitoneal mesothelial cellgastric cancermetastatic dissemination |
spellingShingle | Teruaki Oku Kentaro Shimada Hiroki Kenmotsu Yusuke Ando Chisato Kurisaka Rikio Sano Makoto Tsuiji Shinya Hasegawa Tetsuya Fukui Tsutomu Tsuji Stimulation of Peritoneal Mesothelial Cells to Secrete Matrix Metalloproteinase-9 (MMP-9) by TNF-α: A Role in the Invasion of Gastric Carcinoma Cells International Journal of Molecular Sciences TNF-α matrix metalloproteinase peritoneal mesothelial cell gastric cancer metastatic dissemination |
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 | TNF-α matrix metalloproteinase peritoneal mesothelial cell gastric cancer metastatic dissemination |
url | https://www.mdpi.com/1422-0067/19/12/3961 |
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