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Annals of Surgical Oncology, Vol 3, Issue 2 144-149, Copyright © 1996 by Society of Surgical Oncology

ARTICLES

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

M. Shabahang, A. E. Buffan, J. M. Nolla, L. M. Schumaker, R. V. Brenner, R. R. Buras, R. J. Nauta and S. R. Evans
Department of Surgery, Lombardi Cancer Research Center, Georgetown University Medical Center, Washington, DC, USA.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.


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