Malignancy-associated hypercalcemia

Hypercalcemia is the most frequent paraneoplastic syndrome observed in cancer patients. This morbidity can be divided into two categories: one is hypercalcemia induced by severe bone metastases; the other the elaboration of hypercalcemic factors by solid tumors, termed humoral hypercalcemia of malignancy (HHM). With regard to humoral factors responsible for HHM, a protein with parathyroid hormone (PTH)-like activity, designated PTH-related protein (PTHrP), was isolated from a cancer cell line established from a hypercalcemic patient's lung cancer tissue, and the structure of PTHrP mRNA was identified. Since the biological activity of PTHrP explained most of the clinical and laboratory findings of HHM patients and recent clinical studies indicated the very close relationship between the development of HHM and the production of PTHrP by tumor, PTHrP is now regarded to be the primary candidate for the actual factor responsible for HHM.