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Antiproliferative effect of the C‐terminal fragments of parathyroid hormone‐related protein, PTHrP‐(107–111) and (107–139), on osteoblastic osteosarcoma cells
Author(s) -
Valín Alvaro,
GarcíaOcaña Adolfo,
De Miguel Fernando,
Sarasa José L.,
Esbrit Pedro
Publication year - 1997
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199702)170:2<209::aid-jcp13>3.0.co;2-c
Subject(s) - parathyroid hormone related protein , autocrine signalling , chemistry , parathyroid hormone , bone resorption , medicine , cyclic adenosine monophosphate , endocrinology , osteosarcoma , adenosine , secretion , receptor , cancer research , biochemistry , calcium , biology , organic chemistry
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)NH 2 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. [Tyr 34 ]hPTHrP (1–34)NH 2 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. J. Cell. Physiol. 170:209–215, 1997. © 1997 Wiley‐Liss, Inc.