Phage display selection of peptides that affect prostate carcinoma cells attachment and invasion

BACKGROUND. Prostate cancer-specific proteins must be identified to serve a s diagnostic and prognostic markers. Cell surface proteins are especially i mportant, because they have potential utility as diagnostic markers and the rapeutic targets. Identification of ligands for these proteins will allow u se of these ligands as diagnostic and therapeutic tools and permit the inve stigation of receptor function. We performed a search for peptide ligands t o prostate cancer cell-specific receptors. METHODS. Peptide phage display library was used to isolate specific ligands to LNCaP prostate carcinoma cells receptors. Selected phage and cognate pe ptides were investigated for their cancer-related functions, such as the ab ility to interfere with cell adhesion, spreading, motility, and invasion. RESULTS. Phage designated pg35, blocked spreading of LNCaP cells and their derivatives C4-2 and C4-2b. Cognate peptide did not inhibit spreading, but incubation of C4-2 and C4-2b cells with cognate peptide increased their aff inity for endothelial cells and invasiveness. In addition, the peptide acti vates matrix metalloproteinase (MMP)-2 and 9 in C4-2 and C4-2b cells. CONCLUSIONS. These results indicate that identified ligands may play a role in tumorigenicity and metastatic transformation of prostate cancer. To our knowledge, this is the first identification of a functional cancer-specifi c peptide ligand using the phage display approach. (C) 2001 Wiley-Liss, Inc .