CA2+ Receptor, Prostate Cancer and Bone Metastases
Abstract
While bony metastases of prostate cancer are often osteoblastic, excessive bone resorption also occurs, which contributes to skeletal complications (e.g., pain, fractures) . This research evaluates whether prostate cancer cells express the extracellular calcium (Ca2+0) - 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+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 Ca2+0-induced stimulation of PTHrP secretion, (3) the CaSR transactivates the 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 most of tasks 1 and 2, demonstrated that the CaSR likely trans activates the CaSR in task 3 and initiated the development of 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, 2003
- Accession Number
- ADA414805
Entities
People
- Edward M. Brown
Organizations
- Brigham and Women's Hospital