We have purified
peptides with PTH-like bioactivity from a rat
Leydig cell tumor (H-500) and a human
squamous cell carcinoma, both associated with a syndrome of humor-induced
hypercalcemia.
Tumor extracts were shown to be active in an in vitro renal cytochemical bioassay and in an in vitro
osteosarcoma cell (UMR 108)
adenylate cyclase assay; activity in both assays could be reduced by the PTH antagonist [
norleucine-8,18,
tyrosine-34]bovine PTH-(3-34)-amide. Partially purified extracts of both
tumors and of rat
tumor-
conditioned culture medium were active in vivo in thyroparathyroidectomized rats in preventing
hypocalcemia and increasing fractional
phosphorus excretion and cAMP excretion. Ion exchange chromatography demonstrated that active
peptides were basic in character. Employing reverse phase HPLC and gel permeation HPLC, active
peptides of approximately 9,000 and 9,500 daltons were purified from extracts of the human and rat
tumors, respectively, which had similar but not identical compositions. Two additional bioactive
peptides were detected in rat
tumor extract, and the more active had a mol wt of approximately 28,000. The results demonstrate that
peptides that mimic PTH in a variety of in vivo and in vitro bioassays can be extracted from
malignancies associated with
hypercalcemia, that multiple molecular species may be detected in
tumors that demonstrate PTH-like activity, and that at least one of these
peptides may be similar in two
tumors of highly divergent cell and species origin.