Abstract
Ascites sarcoma 180 (S180A) is a transplantable tumor that induces hypercalcemia in tumor-bearing mice without producing parathyroid hormone-related protein (PTHrP) and stimulates bone resorption in cultured neonatal mouse calvaria. To investigate the effects of S180A on bone formation, bone marrow cells were cultured in the presence of ascorbic acid, dexamethasone and β -glycerophosphate and then cell proliferation and mineralized nodule formation were evaluated. Serum-free conditioned media of ascites cell cultures greatly stimulated the 3H-thymidine uptake (5.5-fold on day 10) throughout the experimental period up to 14 days. On the other hand, they limited the rise in alkaline phosphatase activity significantly compared to control (44.1% and 70.8% of control on day 10 and 14, respectively) . After 14 days of culture, many mineralized nodules were observed in control and recombinant human TGF groups, whereas nodule formation was completely abolished by the addition of S180A CM. Thus the results of the present study indicate that tumor-produced factors cause hypercalcemia by inhibiting bone formation, which cooperates with the stimulation of bone resorption in S180A-bearing mice.
