Antiproliferative effect of the C-terminal fragments of parathyroid hormone-related protein, PTHrP-(107-111) and (107-139), on osteoblastic osteosarcoma cells.
The C-terminal region of parathyroid hormone-related protein (PTHrP) containing the sequence (107-111) appears to be a potent inhibitor of osteoclastic bone resorption. In the present study, we have investigated the effect of human (h)PTHrP (107-139) and hPTHrP (107-111)NH2 on the proliferation of osteoblastic rat osteosarcoma UMR 106 cells. We found that both C-terminal PTHrP peptides, like hPTHrP (1-141), were antimitogenic for these cells, between 1 pM and 10 nM. [Tyr34]hPTHrP (1-34)NH2 was as potent as these peptides but less effective as growth inhibitor in these cells. UMR 106 cells were found to produce and secrete immunoreactive PTHrP. Addition of anti-PTHrP neutralizing antibodies to C- and N-terminal epitopes of PTHrP increased the growth of these cells. Our data suggest that the antiproliferative effect of these C-terminal PTHrP analogs may be independent of cyclic adenosine 3':5'-monophosphate (cAMP) and mediated by protein kinase C. These findings support an autocrine role of PTHrP in bone metabolism.
Valín
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A
Metabolic Unit Research Laboratory, Fundación Jiménez Díaz, Madrid, Spain.
García-Ocaña
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A
De Miguel
F
F
Sarasa
J L
JL
Esbrit
P
P
D000818:Animals; D001859:Bone Neoplasms; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects; D012516:Osteosarcoma; D010281:Parathyroid Hormone / Q000096:biosynthesis / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D019379:Teriparatide / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C071784:parathyroid hormone-related protein (107-111); D019379:Teriparatide; C066078:parathyroid hormone-related protein (1-141); C071097:parathyroid hormone-related protein (107-139); D017868:Cyclic AMP-Dependent Protein Kinases