Tumor expressed pthrp facilitates prostate cancer-induced osteoblastic lesions

relates with prostate cancer skeletal progression; however, the impact of prostate cancer-derived PTHrP on the microenviron-ment and osteoblastic lesions in skeletal metastasis has not been completely elucidated. In this study, PTHrP overexpressing pros-tate cancer clones were stably established by transfection of full length rat PTHrP cDNA. Expression and secretion of PTHrP were verified by western blotting and IRMA assay. PTHrP over-expressing prostate cancer cells had higher growth rates in vitro, and generated larger tumors when inoculated subcutaneously into athymic mice. The impact of tumor-derived PTHrP on bone was investigated using a vossicle co-implant model. Histology revealed increased bone mass adjacent to PTHrP overexpressing tumor foci, with increased osteoblastogenesis, osteoclastogenesis and angiogenesis. In vitro analysis demonstrated pro-osteoclastic and pro-osteoblastic effects of PTHrP. PTHrP enhanced proliferatio