1alpha,25-Dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) is known to inhibit prostate cancer cells in vitro. Its effects on proliferation in the presence of living bone have not been reported, but are especially relevant since much of the morbidity and mortality associated with prostate cancer is due to metastatic bone disease. We investigated the effect of 1alpha,25(OH)(2)D(3) on MatLyLu-beta(2) cells (MatLyLu cells), a rat prostate cancer line, co-cultured in transwells with living rat calvaria. Cultures of MatLyLu cells with living calvaria treated with 1alpha,25(OH)(2)D(3) exhibited a statistically significant increase in proliferation (range 1.4 to 1.7-fold; p<0.05). Cultures of MatLylu cells alone, with spleen cells, muscle tissue, or with living or inactivated calvarial bone showed no differences in proliferation. To investigate the mechanism for enhanced proliferation, Galardin, a matrix metalloproteinase (MMP) inhibitor, or pamidronate, an antiresorptive agent, was added. Enhanced proliferation was prevented by either agent, but not to an equal extent. The presence of 1alpha,25(OH)(2)D(3) may lead to proteolytic release or activation of growth factors from bone. These results may explain the variability in reports on the in vivo effects of Vitamin D and suggest a potential concern in using Vitamin D or its analogs alone in patients with metastatic prostate cancer.
Animals Bone and Bones