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

• Published in: The Prostate 2001-06, Vol.47 (4), p.239-251
• Main Authors: Romanov, Victor I., Durand, David B., Petrenko, Valery A.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Bacteriophages - metabolism; Carcinoma - drug therapy; Carcinoma - metabolism; Carcinoma - pathology; Cell Adhesion - drug effects; Cell Adhesion - physiology; Cell Movement - drug effects; Cell Movement - physiology; Chemotaxis - physiology; Electrophoresis; Endothelium - physiology; Enzyme Activation; Humans; Ligands; Male; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; metastasis; Mice; Mice, Nude; Molecular Sequence Data; Neoplasm Proteins - metabolism; Neoplasm Proteins - pharmacology; Neoplasm Proteins - physiology; Peptide Library; peptide ligands; phage display; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Sequence Homology, Amino Acid; Substrate Specificity; Tumor Cells, Cultured
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.1068

BACKGROUND Prostate cancer‐specific proteins must be identified to serve as diagnostic and prognostic markers. Cell surface proteins are especially important, because they have potential utility as diagnostic markers and therapeutic targets. Identification of ligands for these proteins will allow use of these ligands as diagnostic and therapeutic tools and permit the investigation of receptor function. We performed a search for peptide ligands to 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 peptides were investigated for their cancer‐related functions, such as the ability 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 affinity for endothelial cells and invasiveness. In addition, the peptide activates 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‐specific peptide ligand using the phage display approach. Prostate 47:239–251, 2001. © 2001 Wiley‐Liss, Inc.