期刊
CANCER LETTERS
卷 442, 期 -, 页码 181-192出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2018.10.027
关键词
Ovarian cancer; Cancer-associated mesothelial cells; Plasminogen activator inhibitor-1; Peritoneal metastasis; Microenvironment
类别
资金
- JSPS KAKENHI Grant [2617H04338]
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 (NF kappa B) pathway in the CAMs, thus tran-scriptionally upregulating the expression of the downstream NF kappa B 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.
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