The Influence of Primary Microenvironment on Prostate Cancer Osteoblastic Bone Lesion Development
Abstract
Loss of the stromal TGF- signaling in the prostate has been shown to initiate prostate cancer (PCa), promote PCa progression, and facilitate the development of mixed osteoblastic/osteolytic bone lesions. However, the effects on bone lesions are found to be transient. We thus focused on delineating the context-dependent role of TGF- signaling in the bone microenvironment effects on PCa bone lesions. Using genetic engineered mouse models, TGF- signaling is cell-specifically knockout (KO) in the prostate fibroblasts and osteoblasts in the bone by Colcre/Tgfbr2 KO, or in the myeloid lineage cells, including osteoclasts in the bone by LysMcre/Tgfbr2 KO. Compared the PCa-induced bone lesions in the KO mice tibiae to the lesions in the Flox mice, we found that PC3-induced osteolytic bone lesions were significantly increased by Colcre/Tgfbr2 KO,but were significantly decreased by LysMcre/Tgfbr2 KO. Our findings suggested that osteoblastic TGF- signaling inhibits PCa bone lesions development, but myeloid TGF- signaling promotes PCa bone lesion development. We further found that basic FGF mediated the effect of increased PC3 bone lesions in Colcre/Tgfbr2 KO mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2015
- Accession Number
- AD1006421
Entities
People
- Xiaohong Li