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

ABSTRACT: 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-specifi

SUBMITTER: Lin SC 

PROVIDER: S-EPMC5512590 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature