Constitutive synthesis of 1,25-dihydroxyvitamin D3 by a human small cell lung cancer cell line

Abstract

One of 16 human small cell lung cancer cell lines examined was shown to synthesize a metabolite resembling 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. The NCI H82 line converted 25-hydroxyvitamin D3 (25OHD3) into a compound indistinguishable from 1,25-(OH)2D3 in 3 different high performance liquid chromatography systems. Electron impact mass spectra for the trimethylsilylethers of the metabolite and authentic 1,25-(OH)2D3 were indistinguishable. Binding to an anti-1,25-(OH)2D3 antibody was identical for the metabolite and authentic 1,25-(OH)2D3, whereas administration to rats in vivo caused equivalent stimulation of calcium transport measured in vitro in duodenal sacs. Activity of the H82 1 alpha-hydroxylase appears to be substrate dependent and is not stimulated by PTH, suggesting that it is similar to the enzyme expressed by activated macrophages and other cell types at extrarenal sites. Inhibition by ketoconazole indicates that, like the renal and extrarenal enzymes, the H82 enzyme is cytochrome P450 dependent. These data indicate that the H82 small cell lung cancer cell line constitutively expresses 25-hydroxyvitamin D3-1 alpha-hydroxylase and can synthesize 1,25-(OH)2D3.