Ascites sarcoma 180, an animal model of humoral hypercalcemia of malignancy, produces a factor(s) exhibiting potent bone-resorbing activity without any parathyroid hormone-like activity
Abstract
Ascites sarcoma 180 (S180A) is a transplantable tumor maintained in ddY mice. In the tumor-bearing mice, the plasma Ca, Pi and acid phosphatase levels increased and the plasma alkaline phosphatase levels decreased. The elevation of plasma Pi levels is unusual in humoral hypercalcemia of malignancy (HHM). To characterize the pathogenesis of HHM in the animals, the biological activities in the serum-free conditioned media (CM) of S180A cell cultures were examined. The S180A CM stimulated bone resorption dose dependently and showed TGF-like, IL-1-like and mitogenic activity. Unlike parathyroid hormone (PTH), the factor(s) failed to stimulate cAMP production by either UMR 106-01 cells or neonatal mouse calvaria at concentrations that stimulate bone resorption. Also, the factor(s) stimulated proliferation of UMR 106-01 cells concomitant with a slight increase in intracellular calcium levels. These results indicate that S180A cells produce a factor(s) responsible for bone resorption which is apparently different from PTH-like activity.
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