title: Establishment of a serum tumor marker for preclinical trials of mouse prostate cancer models.
abstract: Current prostate cancer research in both basic and preclinical trial studies employ genetically engineered mouse models. However, unlike in human prostate cancer patients, rodents have no counterpart of prostatic-specific antigen (PSA) for monitoring prostate cancer initiation and progression. In this study, we established a mouse serum tumor marker from a mouse homologue of human prostate secretory protein of 94 amino acids (PSP94). Immunohistochemistry studies on different histologic grades from both transgenic and knock-in mouse prostate cancer models showed the down-regulation of tissue PSP94 expression (P < 0.001), the same as for PSA and PSP94 in humans. The presence of mouse serum PSP94 was shown by affinity column and immunoprecipitation purification using a polyclonal mouse PSP94 antibody. A competitive ELISA protocol was established to quantify serum PSP94 levels with a sensitivity of 1 ng/mL. Quantified serum levels of mouse PSP94 ranged from 49.84 ng/mL in wild-type mice to 113.86, 400.45, and 930.90 ng/mL in mouse prostatic intraepithelial neoplasia with microinvasion, well differentiated, moderately differentiated, and poorly differentiated prostate cancer genetically engineered prostate cancer mice, respectively (P < 0.01, n = 68). This increase in serum PSP94 is also well correlated with age and tumor weight. Through longitudinal monitoring of serum PSP94 levels of castrated mice (androgen ablation therapy), we found a correlation between responsiveness/refractory prostate tissues and serum PSP94 levels. The utility of mouse serum PSP94 as a marker in hormone therapy was further confirmed by three-dimensional ultrasound imaging. The establishment of the first rodent prostate cancer serum biomarker will greatly facilitate both basic and preclinical research on human prostate cancer.
authors.affiliation: Department of Surgery, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: Isaac Van
authors.initials: IV
authors.lastname: Huizen
authors.forename: Guojun
authors.initials: G
authors.lastname: Wu
authors.forename: Madeleine
authors.initials: M
authors.lastname: Moussa
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Chin
authors.forename: Aaron
authors.initials: A
authors.lastname: Fenster
authors.forename: James C
authors.initials: JC
authors.lastname: Lacefield
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakai
authors.forename: Norman M
authors.initials: NM
authors.lastname: Greenberg
authors.forename: Jim W
authors.initials: JW
authors.lastname: Xuan
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D002986:Clinical Trials as Topic; D018076:DNA, Complementary / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017430:Prostate-Specific Antigen / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis*; D029584:Prostatic Secretory Proteins / Q000097:blood; D011994:Recombinant Proteins / Q000737:chemistry; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D029584:Prostatic Secretory Proteins; D011994:Recombinant Proteins; C043076:beta-microseminoprotein; D017430:Prostate-Specific Antigen