Prostate specific antigen, a 33-kDa serine protease belonging to the kallikrein family of proteases, has been reported to be generated from epithelial cells lining the ducts of the prostate (13
). Because secreted levels of PSA have been reported to correlate directly with prostate size, PSA levels have been used as a biomarker for prostate cancer.
The kallikreins are encoded by a multigene family, which has been extensively documented in both rats (14
), and humans (15
). In the rat, prostate kallikrein expression is androgen-dependent (16
). Interestingly, conserved androgen-responsive elements directing prostate transcription of kallikrein genes have been demonstrated only in humans and dogs, among non-rodent mammals (17
), and in the rat (18
), all of which develop prostate cancer with higher frequency compared with other species.
There is a great need for animal models that replicate aspects of prostate cancer in man. Among relevant aspects is the elaboration of a biomarker, such as PSA. In dogs with prostate adenocarcinoma, only 2 out of 31 cases were found to demonstrate labeling for PSA (19
). Further, xenotransplants of some human prostate cancer cell lines, such as LNCaP, express PSA (20
). With respect to PSA, the LW rat is the only immunocompetent small animal model of prostate cancer in which PSA expression has been demonstrated. An approximately 5-fold increase in serum PSA and 15-fold increase in prostate tissue PSA were demonstrated in LW rats with autochthonous prostate cancer compared to controls and these increases were moderated by γ-linoleic acid, a compound shown to suppress the growth of tumor cells (11
). The anti-PSA antibody used in the present study is a specific reagent that reacts with normal prostate and primary and metastatic human prostate tumor tissue. Normal and hyperplastic prostate tissues and well-differentiated prostatic carcinomas have shown a high incidence of PSA-immunoreactive cells, while poorly differentiated prostate adenocarcinoma tissues demonstrated much greater variability, with a lower incidence of immunoreactive cells within and between tumors (21
). Similarly, the poorly differentiated prostate PAIII adenocarcinomas examined from LW rats in this study demonstrated a relatively low percentage of PSA-immunoreactive cells. It is important to note that normal prostate and seminal vesicle tissues from LW rats were not immunoreactive for PSA. Taken together, these data suggest that PSA-labeling occurs in a small percentage of the poorly differentiated PAIII tumor cells, but not in normal LW rat prostate or seminal vesicle tissues.
In summary, focal immunohistochemical PSA labeling of the PAIII tumors examined in this study supports the idea that the PAIII cell line has a prostatic origin.