PARATHYROID HORMONE-RELATED PROTEIN - A POTENTIAL AUTOCRINE GROWTH-REGULATOR IN HUMAN PROSTATE-CANCER CELL-LINES

Objective. We recently demonstrated that parathyroid hormone-related p rotein (PTHrP) is widely expressed by human prostate cancer tissue, su ggesting that PTHrP might be involved in the growth and development of prostate cancer. To study this further, the production of PTHrP and i ts biologic effect were investigated using human prostate cancer cell lines. Methods. The cell lines used were one androgen-dependent cell l ine, LNCaP, and two androgen-independent cell lines, PC-3 and DU- 1 45 . PTHrP secreted by cancer cells was measured by radioimmunoassay. The effect of PTHrP on DNA synthesis in these cells was determined by thy midine incorporation assay. Results. All cell lines secreted immunodet ectable levels of PTHrP in the culture-conditioned media. PC-3 cells s ecreted significantly higher amounts than the other two cell lines. A synthetic peptide, PTHrP(1-34), stimulated thymidine uptake in PC-3 an d DU-145 cells more than threefold the control under serum-free and st eroid-free conditions, whereas LNCaP was not affected. However, in the presence of dihydrotestosterone, DNA synthesis of LNCaP cells was sti mulated by PTHrP in a dose-dependent manner. Additionally, this PTHrP- induced DNA synthesis was completely neutralized by a validated mouse monoclonal antibody (8B12) raised against PTHrP(1-34). Conclusions. Ou r data suggest that PTHrP may play a significant role in the growth of prostate cancer by acting locally in an autocrine fashion.