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Endothelial-to-osteoblast conversion generates osteoblastic metastasis of prostate cancer
- Publication Year :
- 2017
-
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 (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.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Cellular differentiation
Mice, Transgenic
Bone Neoplasms
Bone Morphogenetic Protein 4
Mice, SCID
Biology
General Biochemistry, Genetics and Molecular Biology
Article
Mice
03 medical and health sciences
Prostate cancer
Paracrine signalling
0302 clinical medicine
Internal medicine
Cell Line, Tumor
Biomarkers, Tumor
Tumor Cells, Cultured
medicine
Animals
Humans
Molecular Biology
Neoplasm Staging
Osteoblasts
Osteoblastic metastasis
Bone metastasis
Endothelial Cells
Prostatic Neoplasms
Cell Differentiation
Osteoblast
Cell Biology
Prognosis
medicine.disease
Xenograft Model Antitumor Assays
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Bone morphogenetic protein 4
Culture Media, Conditioned
030220 oncology & carcinogenesis
Cancer research
Subcutaneous implantation
Endothelium, Vascular
Developmental Biology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....bc9bc3cbc8f96635fb6cbd087dc4c9ab