Targeting the Tumor Extracellular Matrix of Prostate Cancer with the Clot-binding Peptides CLT1 and CLT2

摘要

Hormone refractory prostate cancer is virtually incurable as it responds only poorly to conventional chemo- and radiation therapy. It is our goal to improve the overall outcome of prostate cancer through targeted delivery of drugs which are conjugated to homing peptides with high affinity for specific binding sites expressed in prostate tumors. We recently identified two peptides, CLT1 (CGLIIQKNEC) and CLT2 (CNAGESSKNC), that accumulate in tumor interstitial spaces where they appear to associate with proteins specific for plasma clotting. The scope of this grant was to analyze the interaction of CLT1 and 2 with the prostate tumor extracellular matrix. To this end, we performed an in vivo alanine scan to identify the amino acid sequence that mediates binding of CLT and CLT2 to the prostate tumor stroma. So far, our results suggest that AKN is part of the CLT1 tumor homing motif. Further studies are needed to confirm this result and to determine the CLT2 tumor binding function.