Selection and identification of ligand peptides targeting a model of castrate-resistant osteogenic prostate cancer and their receptors.
Proc Natl Acad Sci U S A
; 112(12): 3776-81, 2015 Mar 24.
Article
em En
| MEDLINE
| ID: mdl-25762070
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.
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Base de dados:
MEDLINE
Assunto principal:
Osteogênese
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Peptídeos
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Neoplasias Ósseas
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Neoplasias de Próstata Resistentes à Castração
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article