Features of hyperparathyroidism have long been associated with malignancy, and with the advent of sufficiently sensitive bioassays, parathyroid hormone (PTH)-like activity was recognised in extracts of tumours from patients suffering from humoral hypercalcaemia of malignancy (HHM) (Stewart et al. 1983). While these extracts exhibited actions on bone and kidney that were very similar to those of PTH, low or undetectable levels of immunoreactive PTH in patients' plasma and in the tumour extracts indicated that the substance was unique (Stewart et al. 1980, Rodan et al. 1983, Stewart et al. 1983, Strewler et al. 1983). Subsequently, parathyroid hormone-related protein (PTHrP) was purified, sequenced and cloned from a human lung cancer cell line derived from a patient with HHM (Moseley et al. 1987, Suva et al. 1987).
This protein, homologous with PTH in the amino-terminal region, acts through a common PTH/PTHrP receptor (Jüppner et al. 1991) to promote bone
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