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

doi:10.1016/j.devcel.2017.05.005

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

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66 Scopus citations

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^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.

Original language	English (US)
Pages (from-to)	467-480.e3
Journal	Developmental cell
Volume	41
Issue number	5
DOIs	https://doi.org/10.1016/j.devcel.2017.05.005
State	Published - Jun 5 2017

Keywords

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

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

MD Anderson CCSG core facilities

Functional Genomics Core
Research Animal Support Facility
Small Animal Imaging Facility
Tissue Biospecimen and Pathology Resource

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10.1016/j.devcel.2017.05.005

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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

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, vol. 41, no. 5, pp. 467-480.e3. https://doi.org/10.1016/j.devcel.2017.05.005

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title = "Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer",

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.",

keywords = "bone metastasis, endothelial-to-osteoblast conversion, osteoblast, paracrine factors, prostate cancer, proteomics",

author = "Lin, {Song Chang} and Lee, {Yu Chen} and Guoyu Yu and Cheng, {Chien Jui} and Xin Zhou and Khoi Chu and Monzur Murshed and Le, {Nhat Tu} and Laura Baseler and Abe, {Jun ichi} and Keigi Fujiwara and Benoit deCrombrugghe and Logothetis, {Christopher J.} and Gallick, {Gary E.} and Yu-Lee, {Li Yuan} and Maity, {Sankar N.} and Lin, {Sue Hwa}",

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doi = "10.1016/j.devcel.2017.05.005",

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AU - Lin, Song Chang

AU - Lee, Yu Chen

AU - Yu, Guoyu

AU - Cheng, Chien Jui

AU - Zhou, Xin

AU - Chu, Khoi

AU - Murshed, Monzur

AU - Le, Nhat Tu

AU - Baseler, Laura

AU - Abe, Jun ichi

AU - Fujiwara, Keigi

AU - deCrombrugghe, Benoit

AU - Logothetis, Christopher J.

AU - Gallick, Gary E.

AU - Yu-Lee, Li Yuan

AU - Maity, Sankar N.

AU - Lin, Sue Hwa

PY - 2017/6/5

Y1 - 2017/6/5

N2 - 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.

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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KW - endothelial-to-osteoblast conversion

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KW - paracrine factors

KW - prostate cancer

KW - proteomics

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

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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