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) |