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ItemSecretion of prostaglandins as bone-resorbing agents by renal cortical carcinoma in culture.Atkins, D ; Ibbotson, KJ ; Hillier, K ; Hunt, NH ; Hammonds, JC ; Martin, TJ (Springer Science and Business Media LLC, 1977-11)Fragments of human renal carcinoma tissue have been co-cultured with mouse calvaria. In 9/13 cases significant bone resorption occurred whilst in no case did control kidney cause significant resorption. When bone resorption did occur, it could be reduced by inclusion of indomethacin in the culture medium. In some cases when theophylline was included in culture medium to prevent cyclic AMP breakdown, there was enhancement of tumour-induced bone resorption. Control studies without tumour showed that none of the experimental treatments had a direct effect on bone. Radioimmunoassay of prostaglandin E (PGE) levels in pooled culture media showed that tumour fragments produced appreciable amounts of PGE, and that this production was lowered by indomethacin and increased by theophylline. It is concluded that the bone resorption induced by these tumours is due to a prostaglandin, and that prostaglandin production may be controlled by changes in cyclic AMP metabolism.
ItemCalcitonin-responsive adenylate cyclase in a calcitonin-producing human cancer cell line.Hunt, NH ; Ellison, M ; Underwood, JC ; Martin, TJ (Springer Science and Business Media LLC, 1977-06)A calcitonin-responsive adenylate cyclase has been found in a cell line of a poorly differentiated bronchial carcinoma (BEN cells). The cells have previously been shown to secrete an immunoreactive form of calcitonin in culture. Salmon calcitonin (SCT), porcine calcitonin (PCT) and human calcitonin (CT-M) all stimulated adenylate cyclase activity in particulate preparations. CT-M sulphoxide had little effect. The concentrations of the calcitonins required for half the maximum activation of adenylate cyclase were 6-8, 18 and 90 nm respectively. SCT (30pm) and CT-M (60 pm) increased the intracellular concentration of cyclic AMP from 11-2+/-0-2 (s.e.) to 18-2+/-0-2 and 16-7+/-0-2 respectively over a 2-5-min period. SCT (labelled with 125I) bound to particulate preparations of Ben cells, and competition for binding occurred with unlabelled SCT and CT-M. The concentration of SCT required for half the maximum inhibition of [125I]SCT binding was 11 nm. CT-M sulphoxide inhibited only at high concentration (3 micron). The characteristics of the adenylate cyclase response to SCT did not change over the period between cell adhesion (after subculture) and confluence. However, pre-incubation of cells for 4 h with SCT (150 nm) abolished the subsequent adenylate cyclase response of particulate preparations to further hormone. The practical difficulties encountered in purifying and quantifying the large-mol.-wt. form of CT-M secreted by BEN cells has precluded direct investigation of the potential relationship between hormone secretion and the occurrence of the calcitonin receptor. This relationship is discussed in terms of its possible biological significance.