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Establishment of a Serum Tumor Marker for Preclinical Trials of Mouse Prostate Cancer Models

Authors' Affiliations: Departments of ¹ Surgery, ² Pathology and ³ Imaging Research Laboratories, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada; ⁴ Department of Urology, Nagasaki University School of Medicine, Nagasaki, Japan; and ⁵ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington

Requests for reprints: Jim W. Xuan, Urology Research Laboratory, London Health Sciences Centre, 375 South Street, London, Ontario, N6A 4G5, Canada. Phone: 519-667-6682; Fax: 519-432-7367; E-mail: jim.xuan{at}lhsc.on.ca.

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.

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