Prostate-specific antigen (PSA) protein does not affect growth of prostate cancer cells in vitro or prostate cancer xenografts in vivo.
Denmeade SR., Litvinov I., Sokoll LJ., Lilja H., Isaacs JT.
BACKGROUND: Prostate-specific antigen (PSA) is produced in high amounts by normal and malignant prostate cancer cells. PSA is a serine protease with substrates that include semenogelin I and II, insulin-like growth factor binding protein 3, fibronectin, and laminin. PSA, via its enzymatic activity, may play a role in growth, invasion, and metastasis of prostate cancer cells. Recent data also suggest that the PSA protein itself, independent of enzymatic activity, may also function as an endothelial cell-specific inhibitor of angiogenesis. METHODS: Human (PC3, DU145) and rat (AT2, AT6) prostate cancer cell lines were transfected with the full PSA gene encoding preproPSA protein. PSA-producing clones of each cell line were selected and the amount of enzymatically active PSA produced by each cell line determined using a PSA-specific fluorescent peptide substrate. In vitro and in vivo growth characteristics of PSA-producing transfectants were compared to neomycin controls and wild type cells. RESULTS: All selected clones produced and secreted PSA (5-120 ng/ml/10(5) cells). None of the PSA-transfected cell lines produced detectable amounts of enzymatically active PSA. Production of enzymatically inactive PSA by prostate cancer cell lines did not alter growth kinetics in vitro. PSA-producing xenograft doubling times in vivo were similar to neomycin controls and wild type. CONCLUSION: Although recent reports suggest the PSA protein itself may be antiangiogenic, our results demonstrate that production of PSA protein by prostate cancer cells does not significantly alter growth in vitro or in vivo.