Abstract |
In 50-90% of cases, humoral hypercalcemia of malignancy (HHM) is due to tumor secretion of parathyroid hormone-related protein ( PTHrP). Glucocorticoids are sometimes used as calcium lowering agents and there are in vitro results showing that glucocorticoids diminish PTHrP production. In this study we tested whether the serum- calcium-lowering effect of glucocorticoids is due to decreased PTHrP production by the tumor. As an animal and cell culture model we used the Walker carcinosarcoma (WCS) 256, a rat mammary carcinoma cell line producing PTHrP. In vitro, dexamethasone caused a dose-dependent inhibition of PTHrP production, whereby already 1-5 nmol/L revealed a significant decrease by WCS 256 cells. In contrast to these in vitro results, in WCS 256 tumor-bearing rats, dexamethasone (4 mg/kg body weight on day 4, and 1 mg/kg body weight from day 5 until day 7 after WCS transplantation; circulating dexamethasone levels > 20 nmol/L) did not decrease PTHrP production, PTHrP secretion, serum calcium, or tumor weight in vivo. We conclude that, in this PTHrP-mediated model of humoral hypercalcemia of malignancy, glucocorticoids do not decrease PTHrP production and secretion in vivo and do not show a calcium-lowering effect.
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Authors | T Schilling, M Pecherstorfer, E Blind, B Kohl, H Wagner, R Ziegler, F Raue |
Journal | Bone
(Bone)
Vol. 18
Issue 4
Pg. 315-9
(Apr 1996)
ISSN: 8756-3282 [Print] United States |
PMID | 8726387
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Hormonal
- Glucocorticoids
- Parathyroid Hormone-Related Protein
- Proteins
- Dexamethasone
- Calcium
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Topics |
- Analysis of Variance
- Animals
- Antineoplastic Agents, Hormonal
(pharmacology, therapeutic use)
- Calcium
(blood)
- Carcinoma 256, Walker
(drug therapy, metabolism, pathology)
- Dexamethasone
(pharmacology, therapeutic use)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Female
- Glucocorticoids
(pharmacology, therapeutic use)
- Parathyroid Hormone-Related Protein
- Proteins
(drug effects, metabolism)
- Rats
- Rats, Wistar
- Tumor Cells, Cultured
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