The effect of 1, 25-dihydroxyvitamin D3 on the growth of soft-tissue sarcoma cells as mediated by the vitamin D receptor.

Abstract

Soft-tissue sarcomas, malignant neoplasms originating from mesenchymal tissue, are rare but highly aggressive tumors. Present modes of therapy are associated with high rates of recurrence. 1, 25-Dihydroxyvitamin D3, the active metabolite of vitamin D, serves as a potent antiproliferative agent in human cancer cells. In this study, six soft-tissue sarcoma cell lines were analyzed for vitamin D receptor (VDR) expression, which was then correlated with the degree of growth inhibition in response to 1, 25-dihydroxyvitamin D3. These cell lines included rhabdomyosarcoma (HS729, A204), fibrosarcoma (HS913t), synovial sarcoma (SW982), liposarcoma (SW872), and leiomyosarcoma (SKLMS-1). The level of VDR messenger RNA (mRNA) expression was determined using a ribonuclease protection assay, and functional receptor content was determined by using a ligand-binding assay. Growth studies, including [3H]thymidine uptake and growth curves, were performed on two of the six cell lines that expressed the highest and lowest receptor levels. Ribonuclease protection and ligand-binding assays demonstrated variable levels of VDR, with HS729 showing high expression and A204 showing no expression. In HS729, [3H]thymidine uptake was significantly decreased at 10(-7) M (33%) and 10(-6) M (40%) 1, 25-dihydroxyvitamin D3. Growth curve studies showed significant growth inhibition of 55% at 10(-6) M. A204 cells showed no growth inhibition upon treatment with 1, 25-dihydroxyvitamin D3. This study demonstrates the existence of VDR in soft-tissue sarcoma cells and suggests a correlation between the level of VDR in cells and the degree of growth inhibition caused by 1, 25-dihydroxyvitamin D3 which may potentially serve as an alternative form of therapy for soft-tissue sarcomas.