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

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2017 Jun 7

PMID 28586644

Citations 52

Authors

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

Affiliations

Soon will be listed here.

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 (Tie2/Osx/SCID) with endothelial-specific deletion of osteoblast cell-fate determinant OSX compared with bigenic mice (Osx/SCID). Thus, tumor-induced EC-to-OSB conversion is one mechanism that leads to osteoblastic bone metastasis of PCa.

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