Aminopeptidase A is a functional target in angiogenic blood vessels
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Aminopeptidase A is a functional target in angiogenic blood vessels. / Marchiò, Serena; Lahdenranta, Johanna; Schlingemann, Reinier O; Valdembri, Donatella; Wesseling, Pieter; Arap, Marco A; Hajitou, Amin; Ozawa, Michael G; Trepel, Martin; Giordano, Ricardo J; Nanus, David M; Dijkman, Henri B P M; Oosterwijk, Egbert; Sidman, Richard L; Cooper, Max D; Bussolino, Federico; Pasqualini, Renata; Arap, Wadih.
In: CANCER CELL, Vol. 5, No. 2, 02.2004, p. 151-62.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Aminopeptidase A is a functional target in angiogenic blood vessels
AU - Marchiò, Serena
AU - Lahdenranta, Johanna
AU - Schlingemann, Reinier O
AU - Valdembri, Donatella
AU - Wesseling, Pieter
AU - Arap, Marco A
AU - Hajitou, Amin
AU - Ozawa, Michael G
AU - Trepel, Martin
AU - Giordano, Ricardo J
AU - Nanus, David M
AU - Dijkman, Henri B P M
AU - Oosterwijk, Egbert
AU - Sidman, Richard L
AU - Cooper, Max D
AU - Bussolino, Federico
AU - Pasqualini, Renata
AU - Arap, Wadih
PY - 2004/2
Y1 - 2004/2
N2 - 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.
AB - 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.
KW - Amino Acid Motifs
KW - Animals
KW - Blood Vessels
KW - Cell Division
KW - Cell Hypoxia
KW - Cell Movement
KW - Chick Embryo
KW - Endothelial Cells
KW - Enzyme Inhibitors
KW - Glutamyl Aminopeptidase
KW - Growth Substances
KW - Humans
KW - Mice
KW - Mice, Knockout
KW - Microscopy, Fluorescence
KW - Neoplasms
KW - Neovascularization, Pathologic
KW - Peptide Library
KW - Peptides
KW - Protein Binding
KW - Transplantation, Heterologous
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
KW - Research Support, U.S. Gov't, P.H.S.
M3 - SCORING: Journal article
C2 - 14998491
VL - 5
SP - 151
EP - 162
JO - CANCER CELL
JF - CANCER CELL
SN - 1535-6108
IS - 2
ER -