RRC ID 54771
著者 Oku T, Shimada K, Kenmotsu H, Ando Y, Kurisaka C, Sano R, Tsuiji M, Hasegawa S, Fukui T, Tsuji T.
タイトル Stimulation of Peritoneal Mesothelial Cells to Secrete Matrix Metalloproteinase-9 (MMP-9) by TNF-α: A Role in the Invasion of Gastric Carcinoma Cells.
ジャーナル Int J Mol Sci
Abstract 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.
巻・号 19(12)
公開日 2018-12-9
DOI 10.3390/ijms19123961
PII ijms19123961
PMID 30544870
PMC PMC6321609
MeSH Animals Cell Adhesion / drug effects Cell Line, Tumor Culture Media, Conditioned / pharmacology Epithelium / pathology* Matrix Metalloproteinase 2 / genetics Matrix Metalloproteinase 2 / metabolism Matrix Metalloproteinase 9 / genetics Matrix Metalloproteinase 9 / metabolism* Mice Neoplasm Invasiveness Peritoneum / pathology* RNA, Messenger / genetics RNA, Messenger / metabolism Stomach Neoplasms / enzymology* Stomach Neoplasms / pathology* Tumor Necrosis Factor-alpha / pharmacology*
IF 4.183
引用数 6
リソース情報
ヒト・動物細胞 MKN1(RCB1003)