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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)467-480.e3
JournalDevelopmental Cell
Volume41
Issue number5
DOIs
Publication statusPublished - Jun 5 2017

Keywords

  • bone metastasis
  • endothelial-to-osteoblast conversion
  • osteoblast
  • paracrine factors
  • prostate cancer
  • proteomics

ASJC Scopus subject areas

  • Developmental Biology

Fingerprint Dive into the research topics of 'Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer'. Together they form a unique fingerprint.

  • Cite this

    Lin, S. C., Lee, Y. C., Yu, G., Cheng, C. J., Zhou, X., Chu, K., Murshed, M., Le, N. T., Baseler, L., Abe, J. I., Fujiwara, K., deCrombrugghe, B., Logothetis, C. J., Gallick, G. E., Yu-Lee, L. Y., Maity, S. N., & Lin, S. H. (2017). Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer. Developmental Cell, 41(5), 467-480.e3. https://doi.org/10.1016/j.devcel.2017.05.005