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

17 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 (US)
Pages (from-to)467-480.e3
JournalDevelopmental cell
Volume41
Issue number5
DOIs
StatePublished - Jun 5 2017

Fingerprint

Osteoblasts
Prostatic Neoplasms
Bone
Neoplasm Metastasis
Endothelial cells
Endothelial Cells
Tumors
Bone and Bones
Bone Neoplasms
Neoplasms
Heterografts
Conditioned Culture Medium
Osteogenesis

Keywords

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

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer. / Lin, Song-Chang; Lee, Yu-Chen; Yu, Guoyu; Cheng, Chien Jui; Zhou, Xin; Chu, Khoi; Murshed, Monzur; Le, Nhat Tu; Baseler, Laura; Abe, Jun-ichi; Fujiwara, Keigi; deCrombrugghe, Benoit; Logothetis, Christopher J; Gallick, Gary E; Yu-Lee, Li Yuan; Maity, Sankar N; Lin, Sue-Hwa.

In: Developmental cell, Vol. 41, No. 5, 05.06.2017, p. 467-480.e3.

Research output: Contribution to journalArticle

Lin, Song-Chang ; Lee, Yu-Chen ; Yu, Guoyu ; Cheng, Chien Jui ; Zhou, Xin ; Chu, Khoi ; Murshed, Monzur ; Le, Nhat Tu ; Baseler, Laura ; Abe, Jun-ichi ; Fujiwara, Keigi ; deCrombrugghe, Benoit ; Logothetis, Christopher J ; Gallick, Gary E ; Yu-Lee, Li Yuan ; Maity, Sankar N ; Lin, Sue-Hwa. / Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer. In: Developmental cell. 2017 ; Vol. 41, No. 5. pp. 467-480.e3.
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