Ca2 Receptor, Prostate Cancer, and Bone Metastases
Final addendum 16 Feb 2005-15 Feb 2006
BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
Pagination or Media Count:
14. ABSTRACT While bony metastases of prostate cancer are often osteoblastic, excessive bone resorption also occurs in the sites of metastases, which contributes to skeletal complications e.g., pain, fractures. This research evaluates whether prostate cancer cells express the extracellular calcium Ca2 o-sensing receptor CaSR and whether the CaSR in bony metastases of prostate cancer participates in a vicious cycle involving CaSR-mediated secretion of the bone-resorbing cytokine, parathyroid hormone-related protein PTHrP. The secreted PTHrP would promote further bone resorption, thereby increasing Ca2 o locally and stimulating further PTHrP release. The project entails four tasks--namely showing that 1 prostate cancer cells express the CaSR, 2 the CaSR mediates high Ca2 o-induced stimulation of PTHrP secretion, 3 the CaSR transactivates the epidermal growth factor EGF receptor, and 4 CaSR-stimulated PTHrP secretion from prostate cancer cells increases the severity of metastatic bone disease in vivo in mice. We have accomplished tasks 1, 2, and 3 and are still working on developing the stably transfected cell lines needed for the studies in task 4. These results support a role for the CaSR in a vicious cycle that increases the severity of bone resorption in vivo in humans.
- Anatomy and Physiology
- Medicine and Medical Research