2024-03-28T17:22:31Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00027969
2023-01-16T04:20:13Z
499:500:501
PAI-1 secreted from metastatic ovarian cancer cells triggers the tumor-promoting role of the mesothelium in a feedback loop to accelerate peritoneal dissemination
Peng, Yang
Kajiyama, Hiroaki
Yuan, Hong
Nakamura, Kae
Yoshihara, Masato
Yokoi, Akira
Fujikake, Kayo
Yasui, Hiroaki
Yoshikawa, Nobuhisa
Suzuki, Shiro
Senga, Takeshi
Shibata, Kiyosumi
Kikkawa, Fumitaka
open access
© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Ovarian cancer
Cancer-associated mesothelial cells
Plasminogen activator inhibitor-1
Peritoneal metastasis
Microenvironment
The mesothelium, covered by a continuous monolayer of mesothelial cells, is the first protective barrier against metastatic ovarian cancer. However, mesothelial cells release tumor-promoting factors that accelerate the process of peritoneal metastasis. We identified cancer-associated mesothelial cells (CAMs) that had tumor-promoting potential. Here, we found that plasminogen activator inhibitor-1 (PAI-1) induced the formation of CAMs, after which CAMs increasingly secreted the oncogenic factors interleukin-8 (IL-8) and C-X-C motif chemokine ligand 5 (CXCL5), further promoting the metastasis of ovarian cancer cells in a feedback loop. After the formation of CAMs, PAI-1 activated the nuclear factor kappa B (NFκB) pathway in the CAMs, thus transcriptionally upregulating the expression of the downstream NFκB targets IL-8 and CXCL5. Moreover, PAI-1 correlated with peritoneal metastasis in ovarian cancer patients and indicated a poor prognosis. In both ex vivo and in vivo models, after PAI-1 expression was knocked down, the metastasis of ovarian cancer cells decreased significantly. Therefore, targeting PAI-1 may provide a potential target for future therapeutics to prevent the formation of CAMs and alleviate peritoneal metastasis in ovarian cancer patients.
ファイル公開:2020-02-01
Elsevier
2019-02
eng
journal article
AM
http://hdl.handle.net/2237/00030167
https://nagoya.repo.nii.ac.jp/records/27969
https://doi.org/10.1016/j.canlet.2018.10.027
0304-3835
Cancer Letters
442
181
192
https://nagoya.repo.nii.ac.jp/record/27969/files/20190509original_file_of_paper.pdf
application/pdf
9.9 MB
2020-02-01