THE EFFECT OF 1,25-DIHYDROXYVITAMIN-D-3 ON THE GROWTH OF SOFT-TISSUE SARCOMA-CELLS AS MEDIATED BY THE VITAMIN-D-RECEPTOR

Background: Soft-tissue sarcomas, malignant neoplasms originating from mesenchymal tissue, are rare but highly aggressive tumors. Present mo des of therapy are associated with high rates of recurrence. 1,25-Dihy droxyvitamin D-3, the active metabolite of vitamin D, serves as a pote nt antiproliferative agent in human cancer cells. Methods: In this stu dy, six soft-tissue sarcoma cell lines were analyzed for vitamin D rec eptor (VDR) expression, which was then correlated with the degree of g rowth inhibition in response to 1,25-dihydroxyvitamin D-3. These cell lines included rhabdomyosarcoma (HS729, A204), fibrosarcoma (HS913t), synovial sarcoma (SW982), liposarcoma (SW872), and leiomyosarcoma (SKL MS-1). The level of VDR messenger RNA (mRNA) expression was determined using a ribonuclease protection assay, and functional receptor conten t was determined by using a ligand-binding assay. Growth studies, incl uding [H-3]thymidine uptake and growth curves, were performed on two o f the six cell lines that expressed the highest and lowest receptor le vels. Results: Ribonuclease protection and ligand-binding assays demon strated variable levels of VDR, with HS729 showing high expression and A204 showing no expression. In HS729, [H-3]thymidine uptake was signi ficantly decreased at 10(-7) M (33%) and 10(-6) M (40%) 1,25-dihydroxy vitamin D-3. Growth curve studies showed significant growth inhibition of 55% at 10(-6) M. A204 cells showed no growth inhibition upon treat ment with 1,25-dihydroxyvitamin D-3. Conclusion: This study demonstrat es the existence of VDR in soft-tissue sarcoma cells and suggests a co rrelation between the level of VDR in cells and the degree of growth i nhibition caused by 1,25-dihydroxyvitamin D-3 which may potentially se rve as an alternative form of therapy for soft-tissue sarcomas.