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[Cancer Research 60, 722-727, February 1, 2000]
© 2000 American Association for Cancer Research

Tumor Biology

Aminopeptidase N Is a Receptor for Tumor-homing Peptides and a Target for Inhibiting Angiogenesis1

Renata Pasqualini2,4, Erkki Koivunen, Renate Kain, Johanna Lahdenranta2, Michiie Sakamoto3, Anette Stryhn, Richard A. Ashmun, Linda H. Shapiro, Wadih Arap2 and Erkki Ruoslahti4

The Burnham Institute, La Jolla, California 92037; University of Helsinki, Division of Biochemistry, Helsinki, Finland [E. K.]; Institute for Clinical Pathology, Department of Ultrastructural Pathology and Cell Biology, University of Vienna/AKH Wien, A-1090 Vienna, Austria [R. K.]; Institute for Medical Microbiology and Immunology, Panum Institute 18.3.22, DK-2200 Copenhagen, Denmark [A. S.]; Department of Experimental Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105-2794 [R. A. A.]; and Department of Pathology and Laboratory Medicine, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105-2794 [L. H. S.]

Phage that display a surface peptide with the NGR sequence motif home selectively to tumor vasculature in vivo. A drug coupled to an NGR peptide has more potent antitumor effects than the free drug [W. Arap et al., Science (Washington DC), 279: 377–380, 1998]. We show here that the receptor for the NGR peptides in tumor vasculature is aminopeptidase N (APN; also called CD13). NGR phage specifically bound to immunocaptured APN and to cells engineered to express APN on their surface. Antibodies against APN inhibited in vivo tumor homing by the NGR phage. Immunohistochemical staining showed that APN expression is up-regulated in endothelial cells within mouse and human tumors. In another tissue that undergoes angiogenesis, corpus luteum, blood vessels also expressed APN, but APN was not detected in blood vessels of various other normal tissues stained under the same conditions. APN antagonists specifically inhibited angiogenesis in chorioallantoic membranes and in the retina and suppressed tumor growth. Thus, APN is involved in angiogenesis and can serve as a target for delivering drugs into tumors and for inhibiting angiogenesis.




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Cancer Res., February 1, 2002; 62(3): 867 - 874.
[Abstract] [Full Text] [PDF]

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R. PASQUALINI and W. ARAP
Profiling the Molecular Diversity of Blood Vessels
Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 223 - 226.
[Abstract] [PDF]

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 BloodHome page
S. V. Bhagwat, J. Lahdenranta, R. Giordano, W. Arap, R. Pasqualini, and L. H. Shapiro
CD13/APN is activated by angiogenic signals and is essential for capillary tube formation
Blood, February 1, 2001; 97(3): 652 - 659.
[Abstract] [Full Text] [PDF]

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F. D. Hong and G. L. Clayman
Isolation of a Peptide for Targeted Drug Delivery into Human Head and Neck Solid Tumors
Cancer Res., December 1, 2000; 60(23): 6551 - 6556.
[Abstract] [Full Text]


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