The Influence of Primary Microenvironment on Prostate Cancer Osteoblastic Bone Lesion Development
Technical Report,01 Sep 2014,31 Aug 2015
Van Andel Research Institute Grand Rapids United States
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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 osteoblasticosteolytic 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 ColcreTgfbr2 KO, or in the myeloid lineage cells, including osteoclasts in the bone by LysMcreTgfbr2 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 ColcreTgfbr2 KO,but were significantly decreased by LysMcreTgfbr2 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 ColcreTgfbr2 KO mice.