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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)151-162
Number of pages12
JournalCancer Cell
Volume5
Issue number2
DOIs
Publication statusPublished - Feb 2004

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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    Marchiò, S., Lahdenranta, J., Schlingemann, R. O., Valdembri, D., Wesseling, P., Arap, M. A., Hajitou, A., Ozawa, M. G., Trepel, M., Giordano, R. J., Nanus, D. M., Dijkman, H. B. P. M., Oosterwijk, E., Sidman, R. L., Cooper, M. D., Bussolino, F., Pasqualini, R., & Arap, W. (2004). Aminopeptidase A is a functional target in angiogenic blood vessels. Cancer Cell, 5(2), 151-162. https://doi.org/10.1016/S1535-6108(04)00025-X