Frequency and partial characterization of adenylate cyclase-stimulating activity in tumors associated with humoral hypercalcemia of malignancy.

Parathyroid hormone-like adenylate cyclase-stimulating activity (ACSA) has previously been identified in small numbers of tumors or tumor-conditioned tissue culture medium derived from patients or animals with humoral hypercalcemia of malignancy (HHM). We examined the frequency with which this ACSA occurred in a large group of tumor extracts derived from patients with HHM (n = 20), and compared this to three control groups: normocalcemia-associated tumors (n = 20), hypercalcemic control tumors (n = 7), and normal, nonmalignant tissue samples (n = 10). Eighteen of 20 HHM-associated tumor extracts displayed ACSA whereas only 4 of 37 controls contained detectable ACSA. ACSA in one tumor was partially purified, using sequential extraction steps and reverse-phase, high-performance liquid chromatography. Highly purified ACSA (4800-fold) also contained potent in vitro bone-resorbing activity. The molecular weight as assessed by gel filtration was approximately 40,000 D. These findings provide strong support for the thesis that the humoral factor which is responsible for the syndrome of HHM is a parathyroid hormone-like adenylate cyclase-stimulating protein.