title: 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.affiliation: David H. Koch Center, Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
authors.forename: Jami
authors.initials: J
authors.lastname: Mandelin
authors.affiliation: University of New Mexico Cancer Center and Divisions of Molecular Medicine and.
authors.forename: Marina
authors.initials: M
authors.lastname: Cardó-Vila
authors.affiliation: David H. Koch Center, Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
authors.forename: Wouter H P
authors.initials: WH
authors.lastname: Driessen
authors.affiliation: David H. Koch Center, Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
authors.forename: Paul
authors.initials: P
authors.lastname: Mathew
authors.affiliation: David H. Koch Center, Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
authors.forename: Nora M
authors.initials: NM
authors.lastname: Navone
authors.affiliation: David H. Koch Center, Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
authors.forename: Sue-Hwa
authors.initials: SH
authors.lastname: Lin
authors.affiliation: David H. Koch Center, Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
authors.affiliation: University of New Mexico Cancer Center and Divisions of Molecular Medicine and.
authors.forename: Anna Cecilia
authors.initials: AC
authors.lastname: Rietz
authors.affiliation: University of New Mexico Cancer Center and Divisions of Molecular Medicine and.
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Dobroff
authors.affiliation: David H. Koch Center, Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
authors.forename: Bettina
authors.initials: B
authors.lastname: Proneth
authors.affiliation: 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.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Sidman
authors.affiliation: 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.
authors.forename: Renata
authors.initials: R
authors.lastname: Pasqualini
authors.affiliation: 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.
authors.forename: Wadih
authors.initials: W
authors.lastname: Arap
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary*; D045744:Cell Line, Tumor; D002846:Chromatography, Affinity; D018450:Disease Progression; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D016513:Mice, SCID; D036103:Nanotechnology; D009368:Neoplasm Transplantation; D010012:Osteogenesis; D010455:Peptides / Q000737:chemistry*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D040901:Proteomics; D011944:Receptors, Androgen / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D008024:Ligands; D010455:Peptides; D011944:Receptors, Androgen; D000511:alpha-Macroglobulins
keywords: GRP78; ligand receptors; peptides; phage display; tumor targeting