Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer

Song Chang Lin, Yu Chen Lee, Guoyu Yu, Chien Jui Cheng, Xin Zhou, Khoi Chu, Monzur Murshed, Nhat Tu Le, Laura Baseler, Jun ichi Abe, Keigi Fujiwara, Benoit deCrombrugghe, Christopher J. Logothetis, Gary E. Gallick, Li Yuan Yu-Lee, Sankar N. Maity, Sue Hwa Lin

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46 引文 斯高帕斯(Scopus)


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 (Tie2cre/Osxf/f/SCID) with endothelial-specific deletion of osteoblast cell-fate determinant OSX compared with bigenic mice (Osxf/f/SCID). Thus, tumor-induced EC-to-OSB conversion is one mechanism that leads to osteoblastic bone metastasis of PCa.
頁(從 - 到)467-480.e3
期刊Developmental Cell
出版狀態已發佈 - 6月 5 2017

ASJC Scopus subject areas

  • 發展生物學


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