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

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.

authors

Mandelin J,Cardó-Vila M,Driessen WH,Mathew P,Navone NM,Lin SH,Logothetis CJ,Rietz AC,Dobroff AS,Proneth B,Sidman RL,Pasqualini R,Arap W

doi

10.1073/pnas.1500128112

subject

Has Abstract

pub_date

2015-03-24 00:00:00

pages

3776-81

issue

12

eissn

0027-8424

issn

1091-6490

pii

1500128112

journal_volume

112

pub_type

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