Human prostate carcinoma causes hypercalcemia in athymic nude mice and produces a factor with parathyroid hormone-like bioactivity.
The mechanism of the calcium and phosphorus abnormalities associated with metastatic prostate carcinoma (CaP) is not yet understood. A tumor model was recently established in which 9479, a human CaP from a patient with prostate carcinoma-induced osteomalacia, was heterotransplanted into athymic nude mice (ANM). In the present study the effect of 9479 on ANM was evaluated. Serum calcium (Ca), phosphorus (P), parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3(1,25-(OH)2D3) and urinary cAMP were measured. Ca was markedly elevated in ANM bearing 9479 vs. age-matched controls (C); the increased Ca returned to control level after tumor removal. Serum PTH was lower in 9479-bearing ANM vs. C while urinary cAMP and serum 1,25-(OH)2D3 levels were elevated. In the ANM bearing 9479, there was a decrease in serum P vs. C which returned to normal after tumor removal. Fractional P excretion was greater in 9479 animals than C. Extracts of 9479 were examined for the presence of parathyroid hormone-like bioactivity by measuring stimulation of intracellular cAMP in ROS 17/2.8 cells. Cyclic AMP stimulation which was found was shown to be inhibited by the competitive PTH antagonist [8Nle, 18Nle, 34Tyr]bPTH-(3-34) amide. These data suggest tumor induction of parathyroid hormone-like humoral modulation of calcium, phosphate and vitamin D metabolism in vivo associated with a parathyroid hormone-like prostate carcinoma product.
D000818:Animals; D002118:Calcium / Q000032:analysis; D002277:Carcinoma / Q000032:analysis / Q000150:complications* / Q000378:metabolism; D000242:Cyclic AMP / Q000032:analysis; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010281:Parathyroid Hormone / Q000032:analysis / Q000378:metabolism; D010758:Phosphorus / Q000032:analysis; D011471:Prostatic Neoplasms / Q000032:analysis / Q000150:complications* / Q000378:metabolism; D014807:Vitamin D / Q000032:analysis
D010281:Parathyroid Hormone; D014807:Vitamin D; D010758:Phosphorus; D000242:Cyclic AMP; D002118:Calcium