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Antibodies to parathyroid hormone-related protein lower serum calcium in athymic mouse models of malignancy-associated hypercalcemia due to human tumors.

1988; American Society for Clinical Investigation; Volume: 82; Issue: 5 Linguagem: Inglês

10.1172/jci113794

1558-8238

Subhash C. Kukreja, Daniel H. Shevrin, Sarah A. Wimbiscus, Peter R. Ebeling, J. A. Danks, Christine Rodda, William I. Wood, T. John Martin,

Protein Kinase Regulation and GTPase Signaling

A parathyroid hormone-related protein (PTHrP) has recently been isolated from tumors associated with hypercalcemia. In the present study, we tested the effects of neutralizing antisera to the PTHrP on serum calcium and urine cAMP in two animal models of malignancy-associated hypercalcemia. The animal models consisted of (a) a human squamous cell lung cancer and (b) a human laryngeal cancer, both serially carried in athymic mice. The antisera specifically reduced the elevated serum calcium and urinary cAMP levels in the tumor-bearing animals. We conclude that PTHrP plays a major role in the pathogenesis of malignancy-associated hypercalcemia.