Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis

Phage that display a surface peptide with the NGR sequence motif home selec tively to tumor vasculature in vivo. A drug coupled to an NGR peptide has m ore potent antitumor effects than the free drug [W. Arap et at, Science CV( 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 CD 13). NGR phage specifically bound to immunocaptured APN and to cells engine ered to express APN on their surface. Antibodies against APN inhibited in v ivo 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, bloo d vessels also expressed APN, but APN was not detected in blood vessels of various other normal tissues stained under the same conditions. APN antagon ists specifically inhibited angiogenesis in chorioallantoic membranes and i n the retina and suppressed tumor growth. Thus, APN is involved in angiogen esis and can serve as a target for delivering drugs into tumors and for inh ibiting angiogenesis.