Abstract
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.
Highlights
Summary.-Fragments of human renal carcinoma tissue have been co-cultured with mouse calvaria
This paper demonstrates the production of bone-resorbing activity by unselected calciferol (1,95-(OH)2D3) was the gift of Roche Products Ltd, Welwyn Garden City, and prostaglandin E2 (PGE2) the gift of Dr J
In experiments where 1,25-(OH)2D3, PGE2, theophylline or indomethacin were added to culture media, they were dissolved in a small amount of ethanol and added to the medium to give a level of not more than 0-4% ethanol
Summary
These effects is hypercalcaemia due to the production by neoplastic tissue of boneresorbing agents, especially when the tumour readily metastasizes to bone. In co-culture experiments calvaria were placed on the stainless steel grid as usual and surrounded by 4 1-mm explants of control or tumour renal tissue. In experiments where 1,25-(OH)2D3, PGE2, theophylline or indomethacin were added to culture media, they were dissolved in a small amount of ethanol and added to the medium to give a level of not more than 0-4% ethanol. This level of ethanol has been shown previously not to affect the response of bone to PTH (Atkins et al, 1972). PTH levels were measured by radioimmunoassay (Melick and Martin, 1968) using antiserum BW 211/32 (Burroughs Wellcome) and highly purified bovine PTH for labelling and as standard, and cyclic AMP levels were assessed by a specific protein-binding assay (Brown et al, 1971)
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