Matrix metalloproteinases (MMP9 and MMP2) induce the release of vascular endothelial growth factor (VEGF) by ovarian carcinoma cells: Implications for ascites formation

Dorina Belotti, Paola Paganoni, Luigi Manenti, Angela Garofalo, Sergio Marchini, Giulia Taraboletti, Raffaella Giavazzi

Research output: Contribution to journalArticlepeer-review

Abstract

This study investigated the functional interplay between vascular endothelial growth factor (VEGF) and metalloproteinases (MMPs) in ovarian carcinomas. Levels of MMP9 (pro and activated form) and proMMP2 in ascites correlated with VEGF and with the ascitic volume in nude mice bearing human ovarian carcinoma xenografts (HOC22 and HOC8). The MMP inhibitor batimastat (BB-94) reduced VEGF release and ascitic fluid formation. Exogenous, activated MMP9, and, to a lesser extent, MMP2, increased VEGF release by SKOV3 and OVCAR3 ovarian carcinoma cells. The effect was dose and time dependent and inhibited by BB-94. MMP9-released VEGF was biologically active, because it induced endothelial cell motility, and its activity was prevented by the VEGF inhibitor SU5416. Our results indicate that MMPs, mainly MMP9, play a role in the release of biologically active VEGF and consequently in the formation of ascites.

Original languageEnglish
Pages (from-to)5224-5229
Number of pages6
JournalCancer Research
Volume63
Issue number17
Publication statusPublished - Sep 1 2003

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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