Endothelin-1 promotes proteolytic activity of ovarian carcinoma

Clin Sci (Lond). 2002 Aug:103 Suppl 48:306S-309S. doi: 10.1042/CS103S306S.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Endopeptidases / metabolism*
  • Endothelin Receptor Antagonists
  • Endothelin-1 / pharmacology
  • Female
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism*
  • Peptides, Cyclic / therapeutic use
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Plasminogen Activator Inhibitor 2 / metabolism
  • Receptor, Endothelin A
  • Tumor Cells, Cultured
  • Urokinase-Type Plasminogen Activator / metabolism

Substances

  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Peptides, Cyclic
  • Plasminogen Activator Inhibitor 1
  • Plasminogen Activator Inhibitor 2
  • Receptor, Endothelin A
  • Endopeptidases
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • cyclo(Trp-Asp-Pro-Val-Leu)