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

doi:10.1016/S1535-6108(04)00025-X

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Aminopeptidase A is a functional target in angiogenic blood vessels

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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, …

Cancer cell, Vol.5(2), pp.151-162

2004

DOI: https://doi.org/10.1016/S1535-6108(04)00025-X

PMID: 14998491

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.

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Title: Aminopeptidase A is a functional target in angiogenic blood vessels
Creators: Serena Marchiò - The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA
Johanna Lahdenranta - The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA
Reinier O Schlingemann - Ocular Angiogenesis Group, Department of Ophthalmology, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands
Donatella Valdembri - Division of Molecular Angiogenesis, Department of Oncological Sciences, Institute for Cancer Research and Treatment, University of Turin Medical School, Candiolo 10060, Italy
Pieter Wesseling - Department of Pathology, University Medical Center Nijmegen, Nijmegen, 6500 HB, The Netherlands
Marco A Arap - The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA
Amin Hajitou - The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA
Michael G Ozawa - The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA
Martin Trepel - The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA
Ricardo J Giordano - The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA
David M Nanus - Division of Hematology and Medical Oncology, Department of Medicine and the Department of Urology, Weill Medical College of Cornell University, New York, NY 10021 USA
Henri B.P.M Dijkman - Department of Pathology, University Medical Center Nijmegen, Nijmegen, 6500 HB, The Netherlands
Egbert Oosterwijk - Experimental UrologyUniversity Medical Center Nijmegen, Nijmegen, 6500 HB, The Netherlands
Richard L Sidman - Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115 USA
Max D Cooper - Division of Developmental and Clinical Immunology, Departments of Medicine, Pediatrics, and Microbiology, University of Alabama at Birmingham and the Howard Hughes Medical Institute, Birmingham, AL 35294 USA
Federico Bussolino - Division of Molecular Angiogenesis, Department of Oncological Sciences, Institute for Cancer Research and Treatment, University of Turin Medical School, Candiolo 10060, Italy
Renata Pasqualini - The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA
Wadih Arap - The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA
Publication Details: Cancer cell, Vol.5(2), pp.151-162
Date published: 2004
Publisher: Elsevier Inc
Academic Unit: Radiation Oncology; Cancer Institute of New Jersey at University Hospital
Language: English
Resource Type: Journal article
Identifiers: 991031654949604646