OBJECTIVE: We recently demonstrated that parathyroid hormone-related protein (PTHrP) is widely expressed by human prostate cancer tissue, suggesting that PTHrP might be involved in the growth and development of prostate cancer. To study this further, the production of PTHrP and its biologic effect were investigated using human prostate cancer cell lines. METHODS: The cell lines used were one androgen-dependent cell line, LNCaP, and two androgen-independent cell lines, PC-3 and DU-145. PTHrP secreted by cancer cells was measured by radioimmunoassay. The effect of PTHrP on DNA synthesis in these cells was determined by thymidine incorporation assay. RESULTS: All cell lines secreted immunodetectable levels of PTHrP in the culture-conditioned media. PC-3 cells secreted significantly higher amounts than the other two cell lines. A synthetic peptide, PTHrP(1-34), stimulated thymidine uptake in PC-3 and DU-145 cells more than threefold the control under serum-free and steroid-free conditions, whereas LNCaP was not affected. However, in the presence of dihydrotestosterone, DNA synthesis of LNCaP cells was stimulated 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: Our data suggest that PTHrP may play a significant role in the growth of prostate cancer by acting locally in an autocrine fashion.
OBJECTIVE: We recently demonstrated that parathyroid hormone-related protein (PTHrP) is widely expressed by humanprostate cancer tissue, suggesting that PTHrP might be involved in the growth and development of prostate cancer. To study this further, the production of PTHrP and its biologic effect were investigated using humanprostate cancer cell lines. METHODS: The cell lines used were one androgen-dependent cell line, LNCaP, and two androgen-independent cell lines, PC-3 and DU-145. PTHrP secreted by cancer cells was measured by radioimmunoassay. The effect of PTHrP on DNA synthesis in these cells was determined by thymidine incorporation assay. RESULTS: All cell lines secreted immunodetectable levels of PTHrP in the culture-conditioned media. PC-3 cells secreted significantly higher amounts than the other two cell lines. A synthetic peptide, PTHrP(1-34), stimulated thymidine uptake in PC-3 and DU-145 cells more than threefold the control under serum-free and steroid-free conditions, whereas LNCaP was not affected. However, in the presence of dihydrotestosterone, DNA synthesis of LNCaP cells was stimulated 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: Our data suggest that PTHrP may play a significant role in the growth of prostate cancer by acting locally in an autocrine fashion.
Authors: Primo N Lara; Jeff Longmate; Christopher P Evans; David I Quinn; Przemyslaw Twardowski; Gurkamal Chatta; Edwin Posadas; Walter Stadler; David R Gandara Journal: Anticancer Drugs Date: 2009-03 Impact factor: 2.248