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

研究成果: 雜誌貢獻文章

17 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)467-480.e3
期刊Developmental Cell
41
發行號5
DOIs
出版狀態已發佈 - 六月 5 2017

指紋

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

ASJC Scopus subject areas

  • Developmental Biology

引用此文

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.

於: Developmental Cell, 卷 41, 編號 5, 05.06.2017, p. 467-480.e3.

研究成果: 雜誌貢獻文章

Lin, SC, Lee, YC, Yu, G, Cheng, CJ, Zhou, X, Chu, K, Murshed, M, Le, NT, Baseler, L, Abe, JI, Fujiwara, K, deCrombrugghe, B, Logothetis, CJ, Gallick, GE, Yu-Lee, LY, Maity, SN & Lin, SH 2017, 'Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer', Developmental Cell, 卷 41, 編號 5, 頁 467-480.e3. https://doi.org/10.1016/j.devcel.2017.05.005
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. 於: Developmental Cell. 2017 ; 卷 41, 編號 5. 頁 467-480.e3.
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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.",
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AU - Zhou, Xin

AU - Chu, Khoi

AU - Murshed, Monzur

AU - Le, Nhat Tu

AU - Baseler, Laura

AU - Abe, Jun ichi

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AU - deCrombrugghe, Benoit

AU - Logothetis, Christopher J.

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AU - Lin, Sue Hwa

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AB - 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.

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