Canine prostate stimulates osteoblast function using the endothelin receptors.

摘要: BACKGROUND Bone metastases are common in humans and dogs with late-stage prostate cancer. A unique feature of cancer is new bone formation at metastatic sites (“osteoblastic metastases”). Many carcinomas that metastasize to cause destruction, not formation. The mechanisms by which induces metastasis well understood. We hypothesized stimulation osteoblasts tissue was due the paracrine actions growth factors produced epithelial cells. METHODS We have previously shown normal canine induced when implanted adjacent calvarium nude mice. To complement this vivo model, we developed an vitro system prostate-stimulated osteoblast function investigate prostate-induced formation. RESULTS We found treatment cultured rat calvaria for 24 hr proteins from dog stimulated alkaline phosphatase activity a dose-dependent manner 4–6 fold compared controls. Stimulation began approximately 8 after treatment, diminished 72 hr. Calvaria treated homogenates salivary gland, kidney, bladder, muscle did increase ALP activity. Pretreatment 1 endothelin antagonists, but anti-parathyroid hormone-related protein (PTHrP) antibody or indomethacin, abrogated ALP. CONCLUSIONS Our results indicated activation occurs via endothelin-dependent mechanism, PTHrP prostaglandin synthase-mediated pathways likely involved. This reliable, reproducible assay determining roles molecules important prostate. © 2004 Wileey-Liss, Inc.