| First Author | Lin SC | Year | 2017 |
| Journal | Dev Cell | Volume | 41 |
| Issue | 5 | Pages | 467-480.e3 |
| PubMed ID | 28586644 | Mgi Jnum | J:253614 |
| Mgi Id | MGI:6109821 | Doi | 10.1016/j.devcel.2017.05.005 |
| Citation | Lin SC, et al. (2017) Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer. Dev Cell 41(5):467-480.e3 |
| abstractText | 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. |
