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 Navone; Sue-Hwa Lin; Christopher J Logothetis; Anna Cecilia Rietz; Andrey S Dobroff; Bettina Proneth; Richard L Sidman; Renata Pasqualini; Wadih Arap

doi:10.1073/pnas.1500128112

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

Journal article

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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 Navone, Sue-Hwa Lin, Christopher J Logothetis, Anna Cecilia Rietz, Andrey S Dobroff, Bettina Proneth, …

Proceedings of the National Academy of Sciences - PNAS, Vol.112(12), pp.3776-3781

03/24/2015

DOI: https://doi.org/10.1073/pnas.1500128112

PMCID: PMC4378428

PMID: 25762070

Abstract

Neoplasm Transplantation

Peptides - chemistry

Heat-Shock Proteins - metabolism

Humans

Receptors, Androgen - metabolism

Bone Neoplasms - secondary

Male

Prostatic Neoplasms, Castration-Resistant - drug therapy

Mice, SCID

Prostatic Neoplasms, Castration-Resistant - metabolism

Disease Progression

Prostatic Neoplasms, Castration-Resistant - pathology

alpha-Macroglobulins - metabolism

Animals

Chromatography, Affinity

Drug Design

Proteomics

Cell Line, Tumor

Protein Binding

Ligands

Mice

Nanotechnology

Osteogenesis

Drug Screening Assays, Antitumor

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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Title: Selection and identification of ligand peptides targeting a model of castrate-resistant osteogenic prostate cancer and their receptors
Creators: Jami Mandelin - David H. Koch Center, Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030
Marina Cardó-Vila - University of New Mexico Cancer Center and Divisions of Molecular Medicine and
Wouter H P Driessen - David H. Koch Center, Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030
Paul Mathew - David H. Koch Center, Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030
Nora M Navone - David H. Koch Center, Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030
Sue-Hwa Lin - David H. Koch Center, Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030
Christopher J Logothetis - David H. Koch Center, Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030
Anna Cecilia Rietz - University of New Mexico Cancer Center and Divisions of Molecular Medicine and
Andrey S Dobroff - University of New Mexico Cancer Center and Divisions of Molecular Medicine and
Bettina Proneth - David H. Koch Center, Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030
Richard L Sidman - Harvard Medical School and Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215 richard_sidman@hms.harvard.edu rpasqual@salud.unm.edu warap@salud.unm.edu
Renata Pasqualini - University of New Mexico Cancer Center and Divisions of Molecular Medicine and richard_sidman@hms.harvard.edu rpasqual@salud.unm.edu warap@salud.unm.edu
Wadih Arap - University of New Mexico Cancer Center and Hematology and Oncology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131; and richard_sidman@hms.harvard.edu rpasqual@salud.unm.edu warap@salud.unm.edu
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.112(12), pp.3776-3781
Date published: 03/24/2015
Academic Unit: Radiation Oncology; Cancer Institute of New Jersey at University Hospital
Language: English
Resource Type: Journal article
Identifiers: 991031654607604646