Ca2+ Receptor, Prostate Cancer, and Bone Metastases
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 (Ca(exp 2+ sub 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 Ca(exp 2+ sub o)+0 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 Ca(exp 2+ sub o)+0-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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2005
- Accession Number
- ADA437141
Entities
People
- Edward M. Brown
Organizations
- Brigham and Women's Hospital