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

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.

Developmental cell. 2017 Jun 05 [Epub]

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

Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Pathology, Taipei Medical University and Hospital, Taipei 110, Taiwan., Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Medicine, McGill University, Montreal, QC, H3A 1G1, Canada., Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA., Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: .