Prostate Cancer Skeletal Metastases: Pathobiology and Inventions
Abstract
Prostate cancer skeletal metastases are considered osteoblastic; however, histopathological examination usually reveals underlying osteoclastic activity. A key molecule required for induction of osteoclastic activity is receptor activator of NFkB ligand (RANKL). RANKL activity is opposed by osteoprotegerin (OPG). Thus, the balance of RANKL and OPG in the prostate cancer tissue may regulate the overall phenotype of the metastatic lesion. We are testing the hypothesis that an increase in the RANKL:OPG ratio contributes to the development of CaP skeletal metastases and a corollary hypothesis is that restoring the RANKL:OPG axis through inhibition of RANKL activity will diminish progression of skeletal metastases. In this report, we summarize our work that demonstrates blocking RANKL with sRANK-Fc diminishes progression of human prostate cancer in human bone implanted in mice. Additonally, we demonstrate that the RANKL promoter is active in bone and induced by transforming growth factor-beta (TGF-beta).
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2004
- Accession Number
- ADA424002
Entities
People
- Evan T Keller
Organizations
- University of Michigan