Aminopeptidase A is a functional target in angiogenic blood vessels

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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

133 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)151-162
Aantal pagina's12
TijdschriftCancer Cell
Volume5
Nummer van het tijdschrift2
DOI's
StatusGepubliceerd - feb. 2004
Extern gepubliceerdJa

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