Effect of COX-2 (PGE2) and IL-6 on Prostate Cancer Bone Mets
Abstract
We hypothesize that (1) prostate cancer cells that express cyclooxygenase-2 (COX-2), prostaglandin E2(PGE2) and interleukin-6 (IL-6) display enhanced bone targeting and (2) the level of expression of COX-2, PGE2 and IL-6 in established bone metastases determines the overall bone response, with lower vs. higher cytokine levels inducing osteoblastic vs. osteolytic responses, respectively. We utilize two human prostate cancer cell lines (MDA-PCa-2B that expresses low levels of COX-2 and PGE2 and produces osteoblastic lesions vs. PC-3 that expresses high levels COX-2/PGE2 and induces osteolytic mets). Over the past year, we demonstrated that (1) low levels of PGE2 stimulate preosteoblast cell growth, differentiation and Wnt signaling (2) Forced overexpression of COX-2 in MDA-PCa-2b cells induces the Wnt antagonist DKK-1 (3) PGE2 addition to PC-3 cells stimulates Dkk-1 (4) Forced overexpression of COX-2 in MDA-PCa-2B cells inhibits preosteoblastic cell growth in co-culture. Over the next and final year of the grant proposal we will determine the effects of COX-2/PGE2 expression in the two PCa cell lines on in vivo bone targeting and bone reaction
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2007
- Accession Number
- ADA466562
Entities
People
- Alice C. Levine
Organizations
- Icahn School of Medicine at Mount Sinai