Secretion of parathyroid hormone-like activity from human T-cell lymphotropic virus type I-infected lymphocytes.

Because many patients with adult T-cell leukemia/lymphoma (ATLL) develop hypercalcemia with similar characteristics to those of humoral hypercalcemia of malignancy (HHM) (Arch. Intern. Med., 148: 921-925, 1988), we investigated if ATLL cells produce parathyroid hormone (PTH)-like activity. Conditioned media from cultures of human T-cell lymphotropic virus type I-infected cell line (MT-2) as well as peripheral lymphocytes from a hypercalcemic ATLL patient stimulated cyclic AMP production in osteoblast-like rat osteogenic sarcoma cells (UMR 106) and bone resportion in organ cultures of fetal mouse calvaria. Furthermore, the stimulation of cyclic AMP production by conditioned medium of MT-2 cells was inhibited by human PTH(3-34), indicating that MT-2 cells secrete PTH-like activity. The PTH-like activity from MT-2 cells was chromatographically indistinguishable from the one extracted from a solid tumor causing HHM. The present results along with our previous observation that MT-2 cells constitutively express mRNA for PTH-related protein (Biochem. Biophys. Res. Commun., 154: 1182-1188, 1988) demonstrate that a PTH-like activity is synthesized and secreted by these cells, and are consistent with the hypothesis that elaboration of PTH-like activity by ATLL cells may be the mechanism by which hypercalcemia develops in ATLL patients as well as in solid cancer patients with HHM. However, these results do not rule out the possibility that other factors such as interleukin 1 are also involved and may act in concert with PTH-like activity in the development of hypercalcemia in ATLL.