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.
Original language | English |
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Pages (from-to) | 315-9 |
Number of pages | 5 |
Journal | Bone |
Volume | 18 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr 1996 |
Externally published | Yes |
Keywords
- Analysis of Variance
- Animals
- Antineoplastic Agents, Hormonal/pharmacology
- Calcium/blood
- Carcinoma 256, Walker/drug therapy
- Dexamethasone/pharmacology
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Female
- Glucocorticoids/pharmacology
- Parathyroid Hormone-Related Protein
- Proteins/drug effects
- Rats
- Rats, Wistar
- Tumor Cells, Cultured