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Selection and identification of ligand peptides targeting a model of castrate-resistant osteogenic prostate cancer and their receptors
- Mandelin, Jami, Cardó-Vila, Marina, Driessen, Wouter H. P., Mathew, Paul, Navone, Nora M., Lin, Sue-Hwa, Logothetis, Christopher J., Rietz, Anna Cecilia, Dobroff, Andrey S., Proneth, Bettina, Sidman, Richard L., Pasqualini, Renata, Arap, Wadih
- Proceedings of the National Academy of Sciences of the United States of America 2015 v.112 no.12 pp. 3776-3781
- bacteriophages, drugs, metastasis, models, patients, peptides, prostatic neoplasms, receptors, therapeutics
- We performed combinatorial peptide library screening in vivo on a novel human prostate cancer xenograft that is androgen-independent and induces a robust osteoblastic reaction in bonelike matrix and soft tissue. We found two peptides, PKRGFQD and SNTRVAP, which were enriched in the tumors, targeted the cell surface of androgen-independent prostate cancer cells in vitro, and homed to androgen receptor-null prostate cancer in vivo. Purification of tumor homogenates by affinity chromatography on these peptides and subsequent mass spectrometry revealed a receptor for the peptide PKRGFQD, α-2-macroglobulin, and for SNTRVAP, 78-kDa glucose-regulated protein (GRP78). These results indicate that GRP78 and α-2-macroglobulin are highly active in osteoblastic, androgen-independent prostate cancer in vivo. These previously unidentified ligand–receptor systems should be considered for targeted drug development against human metastatic androgen-independent prostate cancer.