期刊
DEVELOPMENTAL CELL
卷 41, 期 5, 页码 467-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2017.05.005
关键词
-
资金
- NIH [CA174798, P50 CA140388, CA16672]
- Prostate Cancer Foundation
- Cancer Prevention and Research Institute of Texas [CPRIT RP110327, CPRIT RP150179, CPRIT RP150282]
- University Cancer Foundation via the Sister Institute Network Fund at the MD Anderson Cancer Center
- Astellas
- BMS
- Sanofi
- Janssen
- Bayer
- Medivation
Prostate cancer (PCa) bone metastasis is frequently associated with bone-forming lesions, but the source of the osteoblastic lesions remains unclear. We show that the tumor-induced bone derives partly from tumor-associated endothelial cells that have undergone endothelial-to-osteoblast (EC-to-OSB) conversion. The tumor-associated osteoblasts in PCa bone metastasis specimens and patient-derived xenografts (PDXs) were found to co-express endothelial marker Tie-2. BMP4, identified in PDX-conditioned medium, promoted EC-to-OSB conversion of 2H11 endothelial cells. BMP4 overexpression in non-osteogenic C4-2b PCa cells led to ectopic bone formation under subcutaneous implantation. Tumor-induced bone was reduced in trigenic mice (Tie2(cre)/Osx(f/f)/SCID) with endothelial-specific deletion of osteoblast cell-fate determinant OSX compared with bigenic mice (Osx(f/f)/SCID). Thus, tumor-induced EC-to-OSB conversion is one mechanism that leads to osteoblastic bone metastasis of PCa.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据