A new approach, in vivo selection of peptide motifs from phage display libraries for peptides that home specifically to the vasculature of individual tissues or tumors, was developed by the applicant. Homing peptides for the vasculature of a large number of normal tissues and for tumor vasculature have been identify by using this method. Progress has been made recently in identifying some of the molecules (""""""""receptors"""""""") recognized by the homing peptides. The receptors for tumor-homing peptides have been shown to be markers of angiogenic vasculature, and the receptor for a peptide that homes specifically to lung vasculature has been identified. Recent screens have revealed a number of additional tumor-homing peptides for which the receptors remain to be identified. Recent screens have revealed a number of additional tumor-homing peptides for which the receptors remain to be identified. Preliminary results suggest that the tissue-specific vascular markers are lost as blood vessels grow into tumors, while the growing vessels acquire angiogenic markers. The lung-specific peptide receptor serves as a docking site for metastasizing tumor cells in the lung vasculature. The purpose of the research proposed in this component is to identify the receptors for peptides that home to pancreas and prostate vasculature, and to study the expression of the receptors for the various peptides during tumor development. Finally, the tumor cell protein that is responsible fore the binding of the cells to the homing peptide receptor in lung vasculature will be identified. This study will provide new insights to vascular specialization in normal tissues and tumors. New tools for the targeting of therapies will also result from this work.
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