1,25-Dihydroxyvitamin D₃ enhances the growth of tumors in athymic mice inoculated with receptor rich osteosarcoma cells

We tested the influence of daily subcutaneous injections of 12.5 and 25 pmol of 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) on the growth of tumors arising from intracutaneous inoculations of athymic nude mice with rat osteogenic sarcoma cells (ROS) and human melanoma cells. Both doses of 1,25(OH)₂D₃ increased plasma calcium levels after 3 weeks and produced a striking enhancement in tumor weight when the mice received 1,25(OH)₂D₃ receptor-rich ROS17/2.8 cells. In contrast, 1,25(OH)₂D₃ caused no consistent effect on tumor weight in mice given G-361 melanoma cells with low receptor copy number or receptor deficient ROS 24/1 cells. Thus, 1,25(OH)₂D₃ stimulated tumor growth in a receptor dependent fashion, in vivo, instead of inhibiting it as predicted from the reduction of proliferation of cultured cells in the presence of 1,25(OH)₂D₃.