Synthesis of Parathyroid Hormone-Like Peptides by a Human Squamous Cell Carcinoma

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Abstract
Hypercalcemia associated with various types of cancer has been reported by several investigators. In most cases, the postulated cause of the hypercalcemia, ectopic production of parathormone, has been identified only from immunologic measurement of serum or tumor extracts. We have studied the capacity of the malignant tissue from 6 patients with non-parathyroid cancer and hypercalcemia to synthesize parathyroid hormone in vitro. One of these, an esophageal tumor from a 51 year old man which was identified histopathologically as a squamous cell carcinoma, appeared to synthesize peptides(s) with properties similar to parathyroid hormone. Ultrastructural examination of the carcinoma cells revealed the presence of secretory granule-like structures. A sample of tumor tissue slices was incubated with [3H]lysine in a balanced salt solution for 3 h. The tissue was processed by standard procedures for isolation of parathyroid hormone. The resultant tissue extract was gel filtered on G-100 Sephadex. The elution profile contained 5 peaks of radioactivity, one of which was in the region where authentic parathyroid hormone and proparathyroid hormone would elute. Radioimmunoassay of the column eluate with antisera specific for either the amino- or carboxylregion of parathyroid hormone revealed 2 closely associated peaks of immunoreactivity in the parathyroid region. Each of these corresponded approximately to the elution position of a peak of radioactivity. The fractions comprising these 2 peaks of immunoreactivity were pooled separately and subjected to CM-cellulose chromatography together with [14C]bovine parathyroid hormone as marker. Each sample yielded 3 radioactive components upon ion exchange chromatography—one of which co-migrated with the bovine parathyroid hormone marker. Since human parathyroid hormone elutes slightly earlier than the bovine hormone on CM-cellulose, this suggests that the co-migrating tumor peptide is more basic than the glandular human parathyroid hormone. On the basis of the known elution position of proparathyroid hormone from CM-cellulose, it did not appear that the tumor was producing proparathyroid hormone. We conclude that one of the tumors studied synthesized a peptide or peptides similar to but not necessarily identical with glandular parathyroid hormone.

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