Establishment of a serum tumor marker for preclinical trials of mouse prostate cancer models.
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.
Huizen
Isaac Van
IV
Department of Surgery, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
Wu
Guojun
G
Moussa
Madeleine
M
Chin
Joseph L
JL
Fenster
Aaron
A
Lacefield
James C
JC
Sakai
Hideki
H
Greenberg
Norman M
NM
Xuan
Jim W
JW
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
D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D029584:Prostatic Secretory Proteins; D011994:Recombinant Proteins; C043076:beta-microseminoprotein; D017430:Prostate-Specific Antigen