title: Profiling of antibody production against xenograft-released proteins by protein microarrays discovers prostate cancer markers.
abstract: This study describes a novel xenograft-based biomarker discovery platform and proves its usefulness in the discovery of serum markers for prostate cancer. By immunizing immuno-competent mice with serum from nude mice bearing prostate cancer xenografts, an antibody response against xenograft-derived antigens was elicited. By probing protein microarrays with serum from immunized mice, several prostate cancer-derived antigens were identified, of which a subset was successfully retrieved in serum from mice bearing prostate cancer xenografts and prevalidated in human serum samples of prostate cancer patients. Among the discovered and validated proteins were the members of the TAM receptor family (TYRO3, AXL, and MERTK), ACY1, and PSMA1. In conclusion, this novel method allows for the identification of low abundant cancer-derived serum proteins, circumventing dynamic range and host-response issues in standard patient cohort proteomics comparisons.
authors.affiliation: Department of Urology, Erasmus MC , 3000 CA Rotterdam, The Netherlands.
authors.forename: Flip H
authors.initials: FH
authors.lastname: Jansen
authors.forename: Angelique
authors.initials: A
authors.lastname: van Rijswijk
authors.forename: Wilma
authors.initials: W
authors.lastname: Teubel
authors.forename: Wytske M
authors.initials: WM
authors.lastname: van Weerden
authors.forename: Suzanne
authors.initials: S
authors.lastname: Reneman
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: van den Bemd
authors.forename: Monique J
authors.initials: MJ
authors.lastname: Roobol
authors.forename: Chris H
authors.initials: CH
authors.lastname: Bangma
authors.forename: Frank J T
authors.initials: FJ
authors.lastname: Staal
authors.forename: Guido
authors.initials: G
authors.lastname: Jenster
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology / Q000378:metabolism; D000917:Antibody Formation; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000276:immunology*; D040081:Protein Array Analysis; D040901:Proteomics / Q000379:methods*; D012372:ROC Curve; D015203:Reproducibility of Results; D018709:Statistics, Nonparametric; D014183:Transplantation, Heterologous
chemical_list: D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor