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

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261 Citations (Scopus)

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

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Matrix Metalloproteinases
Ascites
Vascular Endothelial Growth Factor A
Carcinoma
Matrix Metalloproteinase Inhibitors
Ascitic Fluid
Metalloproteases
Heterografts
Nude Mice
Cell Movement
Endothelial Cells
batimastat

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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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.",
author = "Dorina Belotti and Paola Paganoni and Luigi Manenti and Angela Garofalo and Sergio Marchini and Giulia Taraboletti and Raffaella Giavazzi",
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T2 - Implications for ascites formation

AU - Belotti, Dorina

AU - Paganoni, Paola

AU - Manenti, Luigi

AU - Garofalo, Angela

AU - Marchini, Sergio

AU - Taraboletti, Giulia

AU - Giavazzi, Raffaella

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