Author/Authors :
Marchiٍ، نويسنده , , Serena and Lahdenranta، نويسنده , , Johanna and Schlingemann، نويسنده , , Reinier O and Valdembri، نويسنده , , Donatella and Wesseling، نويسنده , , Pieter and Arap، نويسنده , , Marco A and Hajitou، نويسنده , , Amin and Ozawa، نويسنده , , Michael G and Trepel، نويسنده , , Martin and Giordano، نويسنده , , Ricardo J and Nanus، نويسنده , , David M and Dijkman، نويسنده , , Henri B.P.M and Oosterwijk، نويسنده , , Egbert and Sidman، نويسنده , , Richard L and Cooper، نويسنده , , Max D and Bussolino، نويسنده , , Federico and Pasqualini، نويسنده , , Renata and Arap، نويسنده , , Wadih، نويسنده ,
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.
