Inhibition of AIDS-Kaposi's sarcoma cell induced endothelial cell invasion by TIMP-2 and a synthetic peptide from the metalloproteinase propeptide: Implications for an anti-angiogenic therapy

Roberto Benelli, Remy Adatia, Barbara Ensoli, William G. Stetler-Stevenson, Leonardo Santi, Adriana Albini

Research output: Contribution to journalArticle

Abstract

In the initial phases of angiogenesis, endothelial cells must degrade and cross the vessel basement membrane, as do tumor cells during invasion and metastasis formation. Various metalloproteinases have been implicated in tumor cell invasion, in particular MMP-2 (72 kDa collagenase IV, gelatinase A), which has been demonstrated to be associated with tumor metastasis formation. Supernatants from AIDS-Kaposi sarcoma (KS) cells induce normal endothelial cells to invade through a reconstituted basement membrane (Matrigel) in vitro, which correlates with the angiogenic potential of KS cells in vivo. Here we demonstrate that two specific inhibitors of MMP-2, TIMP-2 and a peptide from the MMP-2 propeptide region (peptide 74), inhibit endothelial cell invasion induced by ADDS-KS cell Supernatants. Smooth muscle cells were much less sensitive to these inhibitors. These data suggest that MMP-2 activation is a key event in endothelial cell invasion, the initial phase of tumor-associated neoangiogenesis. Inhibition of this enzyme could be an effective treatment for KS and tumor-associated angiogenesis.

Original languageEnglish
Pages (from-to)251-257
Number of pages7
JournalOncology Research
Volume6
Issue number6
Publication statusPublished - 1994

Keywords

  • angiogenesis inhibitors
  • human umbilical vein endothelial cells
  • Kaposi's sarcoma
  • matrix metalloproteinase-2
  • tissue inhibitor of metalloproteases

ASJC Scopus subject areas

  • Cancer Research

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