Endothelin-1 promotes proteolytic activity of ovarian carcinoma.


Endothelin-1 (ET-1) is a potent mitogenic and angiogenic factor for ovarian carcinoma cell lines, which acts selectively through the ET(A) receptor (ET(A)R). 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 ET(A)R, inhibited the ET-1-induced tumour protease secretion and activity, suggesting that ET-1/ET(A)R may play an important role in the progression and metastasis of ovarian carcinoma, activating multiple proteinase cascades.

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@article{Rosan2002Endothelin1PP, title={Endothelin-1 promotes proteolytic activity of ovarian carcinoma.}, author={Laura Rosan{\`o} and Debora Salani and Valeriana Di Castro and Francesca M. Spinella and Pier Giorgio Natali and Anna Bagnato}, journal={Clinical science}, year={2002}, volume={103 Suppl 48}, pages={306S-309S} }