| First Author | Meng X | Year | 2018 |
| Journal | Cancer Lett | Volume | 418 |
| Pages | 109-118 | PubMed ID | 29337106 |
| Mgi Jnum | J:257032 | Mgi Id | MGI:6115689 |
| Doi | 10.1016/j.canlet.2018.01.018 | Citation | Meng X, et al. (2018) Loss of TGF-beta signaling in osteoblasts increases basic-FGF and promotes prostate cancer bone metastasis. Cancer Lett 418:109-118 |
| abstractText | TGF-beta plays a central role in prostate cancer (PCa) bone metastasis, and it is crucial to understand the bone cell-specific role of TGF-beta signaling in this process. Thus, we used knockout (KO) mouse models having deletion of the Tgfbr2 gene specifically in osteoblasts (Tgfbr2(Col1CreERT) KO) or in osteoclasts (Tgfbr2(LysMCre) KO). We found that PCa-induced bone lesion development was promoted in the Tgfbr2(Col1CreERT) KO mice, but was inhibited in the Tgfbr2(LysMCre) KO mice, relative to their respective control Tgfbr2(FloxE2) littermates. Since metastatic PCa cells attach to osteoblasts when colonized in the bone microenvironment, we focused on the mechanistic studies using the Tgfbr2(Col1CreERT) KO mouse model. We found that bFGF was upregulated in osteoblasts from PC3-injected tibiae of Tgfbr2(Col1CreERT) KO mice and correlated with increased tumor cell proliferation, angiogenesis, amounts of cancer-associated fibroblasts and osteoclasts. In vitro studies showed that osteoblastogenesis was inhibited, osteoclastogenesis was stimulated, but PC3 viability was not affected, by bFGF treatments. Lastly, the increased PC3-induced bone lesions in Tgfbr2(Col1CreERT) KO mice were significantly attenuated by blocking bFGF using neutralizing antibody, suggesting bFGF is a promising target inhibiting bone metastasis. |
