Author:
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
Abstract
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.
Publisher
Proceedings of the National Academy of Sciences
Cited by
50 articles.
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