Endothelial cells in tumor vessels express angiogenic markers that are not present in normal vessels. We have developed an in vivo selection system in which phage capable of homing into tumors are recovered from a phage display peptide library following intravenous administration. Using this strategy, we have recently isolated tumor-homing phage displaying the peptide motif asparagine-glycine-arginine (NGR). These NGR-containing peptides bind selectively to angiogenic tumor vessels. A strong candidate receptor for the NGR-containing peptides in tumor vasculature is closely related to CD13/aminopeptidase N (termed NGR receptor). In the work proposed here, we will determine whether the NGR receptor is related or identical to CD13/aminopeptidase. We will investigate its pattern of expression and activity in tumor-induced angiogenesis and determine whether CD13 is also expressed in other forms of angiogenesis. Finally, we will examine the effects of inhibitors of CD13 on tumor growth. These findings will clarify the role of CD13 in angiogenesis and may lead to the development of new anti-tumor therapeutic strategies.
