The hypercalcemic Walker carcinosarcoma 256 of the rat causes an increase in serum 1,25-dihydroxyvitamin D3

We have studied vitamin D metabolism in rats with the transplantable hypercalcemic Walker carcinosarcoma 256, which is a well characterized animal model for humoral hypercalcemia of malignancy. 25-Hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) concentrations were determined in blood samples obtained from parathyroidectomized (PTX) female rats at different time intervals after intramuscular tumor cell inoculation. We observed a dramatic increase in serum 1,25(OH)2D3 (280 +/- 184 vs. 98 +/- 31 pmol/l) 6 days after tumor cell injection and 4 days after the initial rise of serum calcium, whereas 25(OH)D3 tended to decrease. In a separate control experiment we compared this to the effect of exogenous parathyroid hormone in PTX rats and found similar results. In contrast, rats exhibited no change in vitamin D metabolite blood concentration after inoculation of the normocalcemic Yoshida sarcoma, which obviously does not interfere with vitamin D metabolism. We conclude that the humoral bone-resorbing agent produced by the Walker tumor cells causes elevation of serum 1,25(OH)2D3 concentration by this fulfilling an additional criterion of PTH-like activity.