In vivo nuclear uptake of a vitamin D analog (OCT) in different tumor cell populations of FA-6 cancer xenograft in nude mice by receptor autoradiography

Abstract

1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25(OH)2D3] and its analogs have been shown to repress the production of parathyroid hormone-related peptide (PTHrP) in tumors, which is a major factor causing humoral hypercalcemia associated with various cancers. Since vitamin D analogs may be applicable to the treatment of cancer patients, the present study was undertaken to examine whether OCT, an analog with little calcemic activity, is incorporated into tumor tissues, and to identify cellular and subcellular sites of its specific uptake and retention. [26-3H]OCT was injected i.v. into nude mice inoculated with a human pancreatic carcinoma cell line (FA-6). At 1 hour after the injection, intracellular concentration of radioactivity was visualized by receptor (thaw-mount) autoradiography. The results indicate a heterogeneous distribution of radioactivity in nuclei of certain large cancer cells as well as in single or clustered small and elongated cells within the tumor, while connective tissue cells outside of the tumor remained free of nuclear labeling. The data suggest that OCT acts selectively at the genome of cancer cells during a certain maturational stage and also of a second population of small fibroblast-like cells that may have been transplanted with the tumor or are host-derived.