Parathyroid hormone-like adenylate cyclase-stimulating activity from a human carcinoma is associated with bone-resorbing activity.

Abstract

We found previously that a human renal carcinoma cell line derived from a hypercalcemic patient induces humoral hypercalcemia when grown as allografts in the nude mouse and secretes a protein that activates adenylate cyclase via the PTH receptor. The purpose of this study was to examine the conditioned medium of this cell line for bone-resorbing activity in vitro. Processed conditioned medium produced dose-dependent stimulation of bone resorption in cultured fetal rat limb bone explants. Two PTH antagonists were used to assess the PTH receptor dependence of this bone-resorbing activity. Neither [8Nle,18Nle,34Tyr]bovine (b) PTH-(3-34) amide nor [34Tyr]bPTH-(7-34)amide inhibited bone resorption or limb bone cAMP accumulation induced by either processed conditioned medium or equivalent concentrations of bPTH-(1-34). As an alternate means to assess whether this tumor-derived PTH-like protein had intrinsic bone-resorbing activity, the latter was measured during partial purification of PTH-like adenylate cyclase-stimulating activity (ACSA) from conditioned medium by consecutive gel filtration and reverse phase HPLC. The bone-resorbing activity in conditioned medium could not be resolved from PTH-like ACSA by these two separation techniques, indicating that the activities may be intrinsic to the same protein. These results are consistent with the view that a tumor-derived protein with PTH-like ACSA and bone-resorbing activity may be responsible for hypercalcemia in vivo.

• Authors: R F Klein, G J Strewler, S C Leung, R A Nissenson
• Journal: Endocrinology (Endocrinology) Vol. 120 Issue 2 Pg. 504-11 (Feb 1987) ISSN: 0013-7227 [Print] United States
• PMID: 3026777 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Neoplasm Proteins
• Parathyroid Hormone
• Cyclic AMP
• Adenylyl Cyclases

Topics

• Adenocarcinoma (physiopathology)
• Adenylyl Cyclases (pharmacology)
• Animals
• Bone Resorption
• Bone and Bones (drug effects, metabolism)
• Cell Line
• Cyclic AMP (metabolism)
• Fetus
• Humans
• Kidney Neoplasms (physiopathology)
• Kinetics
• Neoplasm Proteins (isolation & purification, pharmacology)
• Organ Culture Techniques
• Parathyroid Hormone (isolation & purification, pharmacology)
• Rats
• Rats, Inbred Strains
• Structure-Activity Relationship