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
N1 - Funding Information:
We thank Drs. A. Joyner and T.J. Langley for reagents and H. Sage and I. J. Fidler for reading of the manuscript. This work was funded by grants from NIH (CA88106, CA078512, CA90270, and CA82976 to R.P.; CA103042, CA90270, CA90810, and DK67683 to W.A.), Juvenile Diabetes Research Foundation (to W.A.), Associazione Italiana per la Ricerca sul Cancro and Istituto Superiore di Sanità (to F.B.), and awards from the Gilson-Longenbaugh Foundation and Angelworks (to R.P. and W.A.). J.L. received fellowships from the Susan G. Komen Breast Cancer Foundation and the Cancer Society of Finland.
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.
UR - http://www.scopus.com/inward/record.url?scp=10744220098&partnerID=8YFLogxK
U2 - 10.1016/S1535-6108(04)00025-X
DO - 10.1016/S1535-6108(04)00025-X
M3 - Article
C2 - 14998491
AN - SCOPUS:10744220098
SN - 1535-6108
VL - 5
SP - 151
EP - 162
JO - Cancer Cell
JF - Cancer Cell
IS - 2
ER -