Aminopeptidase A is a functional target in angiogenic blood vessels.

Abstract	We show that a membrane-associated protease, aminopeptidase A (APA), is upregulated and enzymatically active in blood vessels of human tumors. To gain mechanistic insight, we evaluated angiogenesis in APA null mice. We found that, although these mice develop normally, they fail to mount the expected angiogenic response to hypoxia or growth factors. We then isolated peptide inhibitors of APA from a peptide library and show that they specifically bind to and inhibit APA, suppress migration and proliferation of endothelial cells, inhibit angiogenesis, and home to tumor blood vessels. Finally, we successfully treated tumor-bearing mice with APA binding peptides or anti-APA blocking monoclonal antibodies. These data show that APA is a regulator of blood vessel formation, and can serve as a functional vascular target.
Authors	Serena Marchiò, Johanna Lahdenranta, Reinier O Schlingemann, Donatella Valdembri, Pieter Wesseling, Marco A Arap, Amin Hajitou, Michael G Ozawa, Martin Trepel, Ricardo J Giordano, David M Nanus, Henri B P M Dijkman, Egbert Oosterwijk, Richard L Sidman, Max D Cooper, Federico Bussolino, Renata Pasqualini, Wadih Arap
Journal	Cancer cell (Cancer Cell) Vol. 5 Issue 2 Pg. 151-62 (Feb 2004) ISSN: 1535-6108 [Print] United States
PMID	14998491 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Enzyme Inhibitors Growth Substances Peptide Library Peptides Glutamyl Aminopeptidase
Topics	Amino Acid Motifs Animals Blood Vessels Cell Division Cell Hypoxia (physiology) Cell Movement Chick Embryo Endothelial Cells (physiology) Enzyme Inhibitors Glutamyl Aminopeptidase (metabolism) Growth Substances (metabolism) Humans Mice Mice, Knockout Microscopy, Fluorescence Neoplasms (metabolism) Neovascularization, Pathologic Peptide Library Peptides (metabolism) Protein Binding Transplantation, Heterologous (pathology)

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