EVIDENCE THAT THE BONE RESORPTION-STIMULATING FACTOR PRODUCED BY MOUSE FIBROSARCOMA CELLS IS PROSTAGLANDIN E₂ : A NEW MODEL FOR THE HYPERCALCEMIA OF CANCER

A transplantable mouse fibrosarcoma, HSDM₁, produces a potent bone resorption-stimulating factor. The factor can be extracted from the tumor tissue and harvested from the medium of clonal strains of HSDM₁ tumor cells growing in monolayer culture. It has several chemical and biological properties of a prostaglandin. Using radioimmunoassay techniques, we have shown that HSDM₁ cells synthesize and secrete large quantities of prostaglandin E₂ (PGE₂). The specific bone resorption-stimulating activity of the HSDM₁ factor extracted from the tumor is high and approximately equal to that of PGE₂ as measured in a bone tissue culture system in vitro. Indomethacin, a potent inhibitor of PGE₂ synthesis in HSDM₁ cells, also inhibits production by the cells of the bone resorption-stimulating factor, and has no detectable nonspecific effects on the bone culture assay system. Mice bearing the HSDM₁ tumor have higher levels of both calcium and PGE₂ in serum than control mice. We conclude that PGE₂ is the bone resorption-stimulating factor produced by HSDM₁ tumor cells, and that secretion of PGE₂ by the tumor in vivo accounts for the relative hypercalcemia observed in tumor-bearing animals. The HSDM₁ tumor cell system constitutes a new model for studying the pathogenesis of hypercalcemia associated with certain malignant tumors.