EMERGENCE OF OSTEOBLAST-LIKE CELLS IN A NEOPLASTIC HUMAN SALIVARY CANCER CELL-LINE AFTER TREATMENT WITH 22-OXA-1-ALPHA,25-DIHYDROXYVITAMIN D-3

A neoplastic clonal cell line, which was prepared by 5-azacytidine tre atment of a neoplastic human salivary intercalated duct cell line, was cultivated in the presence of 22-oxa-1 alpha, 25-dihydroxyvitamin D-3 and 3 mM beta-glycerophosphate. Major alterations, such as expression of type 1 collagen and alkaline phosphatase as well as of human osteo pontin and osteonectin, were observed in these cells with a phenotype similar to osteoblasts. In addition, formation of bone nodule was obse rved in the cultured cells. The tumors produced by transplantation int o nude mice of the clonal cells were treated with 22-oxa-1 alpha, 25-d ihydroxyvitamin D-3 and examined for tumor growth and morphology. Cons equently, growth of the treated tumor was significantly suppressed. Mo reover, it was found that bone formation was induced in the treated tu mor, in which the tumor cells around bone formation expressed human os teopontin and osteonectin mRNA as could be detected by in situ hybridi zation. The above findings indicate that the emergence of osteoblast-l ike cells in the human salivary cancer cells occurs in the presence of 22-oxa-1 alpha, 25-dihydroxyvitamin D-3 and beta-glycerophosphate. (C ) 1997 Elsevier Science Ireland Ltd.