Parathyroid hormone-related protein (PTHrP) modulates adhesion, migration and invasion in bone tumor cells

Bone ◽  
2013 ◽  
Vol 55 (1) ◽  
pp. 198-207 ◽  
Author(s):  
Isabella W.Y. Mak ◽  
Robert E. Turcotte ◽  
Michelle Ghert
2005 ◽  
Vol 129 (4) ◽  
pp. 531-533 ◽  
Author(s):  
Lei Chen ◽  
Tri A. Dinh ◽  
Abida Haque

Abstract Small cell carcinoma of the ovary is a rare malignant tumor of the ovary. It is the most common undifferentiated ovarian carcinoma in young women. Approximately two thirds of patients with ovarian small cell carcinoma have hypercalcemia. The mechanism of development of hypercalcemia is unclear, although parathyroid hormone–related protein has been found in some of the cases. Parathormone expression in tumor cells, rarely reported, was seen in this case, suggesting that ectopic parathyroid hormone production by the tumor cells may be the cause of hypercalcemia.


Author(s):  
Jean F. Emly ◽  
Wendy A. Ratcliffe ◽  
Elaine Green ◽  
Sarah J. Bowden ◽  
David A. Heath ◽  
...  

1995 ◽  
Vol 19 (2) ◽  
pp. 292-297 ◽  
Author(s):  
Arnold Tabuenca ◽  
Subburaman Mohan ◽  
Carlos A. Garberoglio ◽  
Patrick I. Borgen ◽  
Thomas Rosol ◽  
...  

2000 ◽  
Vol 166 (1) ◽  
pp. 11-20 ◽  
Author(s):  
P Esbrit ◽  
J Benitez-Verguizas ◽  
F de Miguel ◽  
A Valin ◽  
A Garcia-Ocana

Parathyroid hormone (PTH)-related protein (PTHrP) is the main factor responsible for humoral hypercalcemia of malignancy. Both PTH and PTHrP bind to the common type I PTH/PTHrP receptor (PTHR), thereby activating phospholipase C and adenylate cyclase through various G proteins, in bone and renal cells. However, various normal and transformed cell types, including hypercalcemic Walker 256 (W256) tumor cells, do not produce cAMP after PTHrP stimulation. We characterized the PTHrP receptor and the signaling mechanism upon its activation in the latter cells. Scatchard analysis of PTHrP-binding data in W256 tumor cells revealed the presence of high affinity binding sites with an apparent K(d) of 17 nM, and a density of 90 000 sites/cell. In addition, W256 tumor cells immunostained with an anti-PTHR antibody, recognizing its extracellular domain. Furthermore, reverse transcription followed by PCR, using primers amplifying two different regions in the PTHR cDNA corresponding to the N- and C-terminal domains, yielded products from W256 tumor cell RNA which were identical to the corresponding products obtained from rat kidney RNA. Consistent with our previous findings on cAMP production, 1 microM PTHrP(1-34), in contrast to 10 microg/ml cholera toxin or 1 microM isoproterenol, failed to affect protein kinase A activity in W256 tumor cells. However, in these cells we found a functional PTHR coupling to G(alpha)(q/11), whose presence was demonstrated in these tumor cell membranes by Western blot analysis. Our findings indicate that W256 tumor cells express the PTHR, which seems to be coupled to G(alpha)(q/11). Taken together with previous data, these results support the hypothesis that a switch from the cAMP pathway to the phospholipase C-intracellular calcium pathway, associated with PTHR activation, occurs in malignant cells.


2000 ◽  
pp. 500-505 ◽  
Author(s):  
N Buchs ◽  
D Manen ◽  
JP Bonjour ◽  
R Rizzoli

The production of parathyroid hormone-related protein (PTHrP) is regulated by a variety of hormones and growth factors. Previous research has shown that several PTHrP-producing cells are influenced by extracellular calcium (Ca(2+)(o)) concentration, with elevated levels increasing PTH-like activity released by cultured H500 rat Leydig tumor cells through a post-transcriptional mechanism. We have investigated the hypothesis that calcium stimulates PTHrP production in H500 cells by interacting with a cell membrane-associated cation-sensing receptor. Besides increased Ca(2+)(o) concentration, magnesium and the polycationic antibiotic neomycin also increased PTHrP production in a concentration-dependent manner. In the presence of the calcium ionophore, ionomycin, which markedly elevated cytosolic free calcium, the stimulation by Ca(2+)(o) of PTHrP could still be detected. These results indicate that increasing Ca(2+)(o) stimulates PTHrP production, possibly through a putative cell membrane-associated calcium-sensing mechanism. RT-PCR revealed the presence of a very small amount of calcium-sensing receptor coding mRNA.


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