ASSOCIATION OF HYPERCALCEMIA WITH TUMORS PRODUCING COLONY-STIMULATING FACTOR(S)

Abstract

Two human malignant tumors, previously reported to produce colony-stimulating factors (CSF), were accompanied by remarkable hypercalcemia. A patient with a CSF-producing lower jaw cancer (squamous cell carcinoma) developed a marked granulocytosis (150,000/.mu.l) and hypercalcemia (> 15 mg/dl). The tumor was successfully transplanted into nude mice, which developed marked grnaulocytosis (300,000/.mu.l) and hypercalcemia (20 mg/dl). White blood cell and serum Ca concentrations of these mice decreased promptly to normal levels when the tumor was excised. Treatment with prednisolone (1.5 mg/kg) or indomethacin (5 mg/kg) had no effect on the serum Ca level of these mice. Parathyroid hormone or prostaglandin E was not increased in the serum of the mice or in the tumor tissue. The mice bearing the tumor excreted extremely large amounts of Ca in their urine, and their bony tissues contained less Ca and P than controls. Histology of bony tissues of these nude mice clearly demonstrated the decrease in trabecular tissues and cortical thickness and remarkable activation of osteoclasts. Another patient with a CSF-producing bronchogenic squamous cell carcinoma showed mild granulocytosis and hypercalcemia. The biopsied tumor tissue was transplanted into nude mice, which developed marked granulocytosis (300,000/.mu.l) and severe hypercalcemia (18 mg/dl). The results suggest the presence of a new syndrome of granulocytosis and hypercalcemia associated with CSF-producing tumors. The causal mechanism of the hypercalcemia was some humoral factor which activates osteoclasts other than parathyroid hormone. Neither protaglandins nor the osteoclast-activating factor seemed to be the cause of the hypercalcemia.