Canine lymphosarcoma: a model for study of the hypercalcemia of cancer.

Abstract

Lymphosarcoma of domestic dogs is often accompanied by hypercalcemia. We have carried out studies to determine the usefulness of this common canine neoplasm as a model for paraneoplastic hypercalcemia. The study population consisted of 27 healthy control dogs, 13 with hypercalcemic lymphosarcoma, and 28 normocalcemic dogs with lymphosarcoma. Studies included measurement of circulating calcium, phosphorus, creatinine, immunoreactive parathyroid hormone (iPTH) and prostaglandin E2 (iPGE2) concentrations, and determination of in vitro bone-resorbing activity in supernatant culture media from normal and neoplastic lymphoid tissue. Hypercalcemia was severe in the affected group (mean ± SE, 14.9±0.5 mg/dl, normals 10.1±0.1 mg/dl) and associated with decreased renal function (serum creatinine 2.0±0.4 mg/dl, normal 0.8±0.1 mg/dl,P<0.001). Radiographs and autopsies showed no bone destruction. Despite renal insufficiency, hypercalcemic dogs had subnormal serum iPTH concentrations (12±1 ngEq/ml, normals 37±6 ngEq/ml,P<0.05). Creatinine and iPTH were normal in the normocalcemic tumor-bearing dogs. When antitumor therapy lowered serum calcium to normal or below in 5 hypercalcemic dogs, iPTH rose markedly in all while renal function improved. Plasma iPGE2 levels did not differ among the groups, nor did high-dose oral aspirin or indomethacin treatment lower elevated serum calcium (two dogs). Culture media from normal lymphoid tissue and control culture media had no effect on release of45Ca from prelabeled fetal mouse forelimb bones, but media from tumor tissue increased45Ca release. However, correlation of serum calcium with in vitro bone-resorbing activity was poor. We conclude that (a) the hypercalcemia of canine lymphosarcoma is mediated not by bone metastases or “ectopic” secretion of PTH, but by other bone-resorbing factors secreted by the tumors; and (b) canine lymphosarcoma may be a valuable experimental model for study of some human paraneoplastic hypercalcemias.