Selection and identification of ligand peptides targeting a model of castrate-resistant osteogenic prostate cancer and their receptors

Jami Mandelin, Marina Cardó-Vila, Wouter H.P. Driessen, Paul Mathew, Nora M. Navonea, Sue Hwa Lin, Christopher J. Logothetis, Anna Cecilia Rietz, Andrey S. Dobroff, Bettina Proneth, Richard L.Sidman, Renata Pasqualini, Wadih Arap

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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 bone-like 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.

Original languageEnglish (US)
Pages (from-to)3776-3781
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number12
DOIs
StatePublished - Mar 24 2015
Externally publishedYes

Keywords

  • GRP78
  • Ligand receptors
  • Peptides
  • Phage display
  • Tumor targeting

ASJC Scopus subject areas

  • General

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