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.

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 AIDS-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.
Authors	R Benelli, R Adatia, B Ensoli, W G Stetler-Stevenson, L Santi, A Albini
Journal	Oncology research (Oncol Res) Vol. 6 Issue 6 Pg. 251-7 ( 1994) ISSN: 0965-0407 [Print] United States
PMID	7532474 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Culture Media, Conditioned Drug Combinations Intercellular Signaling Peptides and Proteins Laminin Neoplasm Proteins Peptides Proteins Proteoglycans matrigel Tissue Inhibitor of Metalloproteinase-2 peptide 74 Collagen Cycloheximide Gelatinases Metalloendopeptidases Matrix Metalloproteinase 2
Topics	Acquired Immunodeficiency Syndrome (complications) Amino Acid Sequence Chemotaxis (drug effects) Collagen Culture Media, Conditioned (pharmacology) Cycloheximide (pharmacology) Drug Combinations Endothelium, Vascular (drug effects, pathology) Gelatinases (antagonists & inhibitors, chemistry, physiology) Gene Expression Regulation, Neoplastic (drug effects) Humans Intercellular Signaling Peptides and Proteins Laminin Matrix Metalloproteinase 2 Metalloendopeptidases (antagonists & inhibitors, chemistry, physiology) Molecular Sequence Data Muscle, Smooth, Vascular (drug effects, pathology) Neoplasm Invasiveness Neoplasm Proteins (antagonists & inhibitors, physiology) Neovascularization, Pathologic (drug therapy) Peptides (pharmacology) Proteins (pharmacology) Proteoglycans Sarcoma, Kaposi (blood supply, enzymology, etiology, pathology) Tissue Inhibitor of Metalloproteinase-2 Tumor Cells, Cultured Umbilical Veins

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