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Article

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

1
Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, Japan
2
Department of Health Chemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(12), 3961; https://doi.org/10.3390/ijms19123961
Received: 12 October 2018 / Revised: 6 December 2018 / Accepted: 6 December 2018 / Published: 9 December 2018
(This article belongs to the Special Issue Matrix Metalloproteinase)
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. View Full-Text
Keywords: TNF-α; matrix metalloproteinase; peritoneal mesothelial cell; gastric cancer; metastatic dissemination TNF-α; matrix metalloproteinase; peritoneal mesothelial cell; gastric cancer; metastatic dissemination
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MDPI and ACS Style

Oku, T.; Shimada, K.; Kenmotsu, H.; Ando, Y.; Kurisaka, C.; Sano, R.; Tsuiji, M.; Hasegawa, S.; Fukui, T.; Tsuji, T. Stimulation of Peritoneal Mesothelial Cells to Secrete Matrix Metalloproteinase-9 (MMP-9) by TNF-α: A Role in the Invasion of Gastric Carcinoma Cells. Int. J. Mol. Sci. 2018, 19, 3961. https://doi.org/10.3390/ijms19123961

AMA Style

Oku T, Shimada K, Kenmotsu H, Ando Y, Kurisaka C, Sano R, Tsuiji M, Hasegawa S, Fukui T, Tsuji T. 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. 2018; 19(12):3961. https://doi.org/10.3390/ijms19123961

Chicago/Turabian Style

Oku, Teruaki, Kentaro Shimada, Hiroki Kenmotsu, Yusuke Ando, Chisato Kurisaka, Rikio Sano, Makoto Tsuiji, Shinya Hasegawa, Tetsuya Fukui, and Tsutomu Tsuji. 2018. "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 19, no. 12: 3961. https://doi.org/10.3390/ijms19123961

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