Endothelin-1 (ET-1) is a potent mitogenic and angiogenic factor for ovarian carcinoma cell lines, which acts selectively through the ETA receptor (ETAR). A previous study demonstrated that ET-1 is present at high concentrations in ovarian cancer ascites, indicating a direct role in the progression and metastasis of ovarian carcinoma. In this study, we investigated whether ET-1 could induce production and activation of tumour-associated proteinases in ovarian carcinoma cells. As demonstrated by ELISA, we found that the secretion of matrix metalloproteinase (MMP)-2 and MMP-9, urokinase-type plasminogen activator and plasminogen activator inhibitor type-1 and -2 was upregulated by ET-1 in a dose-dependent manner in the HEY cell line. In addition, the MMPs in ET-1-treated cells are consistently active, as shown by MMP gelatinase activity assay. Finally, we demonstrated that BQ-123, an antagonist of ETAR, inhibited the ET-1-induced tumour protease secretion and activity, suggesting that ET-1/ETAR may play an important role in the progression and metastasis of ovarian carcinoma, activating multiple proteinase cascades.
Endothelin-1 promotes proteolytic activity of ovarian carcinoma
Laura ROSANÒ, Debora SALANI, Valeriana DI CASTRO, Francesca SPINELLA, Pier Giorgio NATALI, Anna BAGNATO; Endothelin-1 promotes proteolytic activity of ovarian carcinoma. Clin Sci (Lond) 1 September 2002; 103 (s2002): 306S–309S. doi: https://doi.org/10.1042/CS103S306S
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