Enhancement of cyclic adenosine monophosphate content in bone cells by the factor extracted from a pancreatic cancer associated with hypercalcemia.

A woman with exocrine pancreatic cancer presented a syndrome of humoral hypercalcemia of malignancy (HHM). Either urea extract or acid/ethanol extract of the tumor showed a dose-dependent activity to elevate cyclic adenosine monophosphate (AMP) level in rat bone cells in primary culture. When each population obtained by the sequential digestion of rat fetal calvaria was cultured individually and cyclic AMP responses to parathyroid hormone (PTH), calcitonin, and tumor extract were examined, tumor extract-sensitive cells showed a similar distribution to PTH-sensitive cells. Tumor extract and PTH, but not calcitonin, increased cyclic AMP in osteogenic cell line MC 3T3-E1. PTH receptor-mediated increase of cyclic AMP was indicated by an antagonistic action of PTH analogue, (3-34) hPTH, on increase of cyclic AMP in MC 3T3-E1 elicited by tumor extract. Human breast cancer derived cell line MCF-7 had calcitonin-sensitive adenylate cyclase, but neither PTH nor tumor extract increased cyclic AMP in the cells. On Bio-Gel P-60 column, the activity to stimulate bone cell cyclic AMP was eluted as a single peak at the molecular size between 6.5 K and 12.4 K. It was concluded that pancreatic cancer, although rather exceptional as a cause of HHM, produced a factor very similar to that reported in representative HHM tumors of human and animal models.