EVIDENCE THAT THE BONE RESORPTION-STIMULATING FACTOR PRODUCED BY MOUSE FIBROSARCOMA CELLS IS PROSTAGLANDIN E2

Abstract

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.