Prostaglandin-mediated hypercalcemia in the VX₂ carcinoma-bearing rabbit

Prostaglandin biosynthesis and metabolism were studied in the VX₂ carcinoma-bearing rabbit, an animal model of prostaglandin-mediated hypercalcemia. All the identification and quantification of the prostaglandins were done by gas chromatography-mass spectrometry. The tumor incubated in vitro converted exogeneous arachidonic acid principally to PGE₂. Biosynthesis from endogenous precursor lipids yields mainly PGE₂ and PGF₂α. The 100,000 × g supernatant fluid of the tumor did not contain any metabolizing enzymes. Significant hypercalcemia developed between the first and second week after tumor implantation. The levels of the major plasma metabolite of PGE₂, 15-keto-13,14-dihydro-PGE₂, became elevated at one week, had risen 25-fold by the end of the second week, and at the fourth week were elevated to 256 times the pre-incubation levels. The concentration of 15-keto-13,14-dihydro-PGF₂α in plasma rose in parallel but to a lesser degree. 7α-hydroxy-5,11-diketotetranor-prostane-1,16-dioic acid, the major urinary metabolite of the E prostaglandins, was elevated two weeks after tumor implantation and rose until the fifth week. Indomethacin treatment lowered both serum calcium and the plasma level of 15-keto-13,14-dihydro-PGE₂.