MOLECULAR-FORMS OF PARATHYROID HORMONE-RELATED PROTEIN IN TUMORS AND BIOLOGICAL-FLUIDS

OBJECTIVE We investigated the content and compared the molecular forms of parathyroid hormone-related protein in tumour tissue, plasma and pleural fluid. DESIGN Measurement of parathyroid hormone-related protein in tumour extracts and biological fluids and comparison of the elution profiles of parathyroid hormone-related protein (PTHRP) immunoreactivity following gel filtration chromatography on Bio-gel P100. PATIENTS Tumours and plasma from patients with humoral hypercalcaemia of malignancy were studied, together with tumours and pleural fluids from patients who were normocalcaemic. MEASUREMENTS immunoreactivity in column fractions, plasma and tumour extracts was measured by a highly sensitive immunoradiometric assay for PTHRP 1-86 with specificity directed at the 17-61 region of PTHRP. RESULTS Similar levels of PTHRP immunoreactivity were measured in tumours from normocalcaemic and hypercalcaemic patients. PTHRP 1-86 (28-4630 fmol/g) was detected in eight of the nine tumours studied. Immunoreactivity in tumour extracts eluted as major peaks in the range 22-33 kDa with an additional peak of 15 kDa in three out of six tumours studied. in contrast, immunoreactivity in plasma and pleural fluid eluted within the range 7-14 kDa. CONCLUSIONS The major species of parathyroid hormone-related protein in plasma and pleural fluids was consistently smaller than that in tumour tissue (22-33 kDa) suggesting that tumour-derived parathyroid hormone-related protein is processed at the COOH-terminus to form a species of approximately 10 kDa which circulates in patients with humoral hypercalcaemia of malignancy.