Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis

Younghun Jung; Jin Koo Kim; Yusuke Shiozawa; Jingcheng Wang; Anjali Mishra; Jeena Joseph; Janice E. Berry; Samantha McGee; Eunsohl Lee; Hongli Sun; Jianhua Wang; Taocong Jin; Honglai Zhang; Jinlu Dai; Paul H. Krebsbach; Evan T. Keller; Kenneth J. Pienta; Russell S. Taichman

doi:10.1038/ncomms2766

Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis

Younghun Jung, Jin Koo Kim, Yusuke Shiozawa, Jingcheng Wang, Anjali Mishra, Jeena Joseph, Janice E. Berry, Samantha McGee, Eunsohl Lee, Hongli Sun, Jianhua Wang, Taocong Jin, Honglai Zhang, Jinlu Dai, Paul H. Krebsbach, Evan T. Keller, Kenneth J. Pienta, Russell S. Taichman

Research output: Contribution to journal › Article › peer-review

227 Scopus citations

Abstract

Tumours recruit mesenchymal stem cells to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that CXCL16, a ligand for CXCR6, facilitates mesenchymal stem cell or very small embryonic-like cells recruitment into prostate tumours. CXCR6 signalling stimulates the conversion of mesenchymal stem cells into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also known as CXCL12. CXCL12 expressed by cancer-associated fibroblasts then binds to CXCR4 on tumour cells and induces an epithelial-to-mesenchymal transition, which ultimately promotes metastasis to secondary tumour sites. Our results provide the molecular basis for mesenchymal stem cell recruitment into tumours and how this process leads to tumour metastasis.

Original language	English (US)
Article number	1795
Journal	Nature communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms2766
State	Published - 2013
Externally published	Yes

ASJC Scopus subject areas

Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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10.1038/ncomms2766

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Jung, Y., Kim, J. K., Shiozawa, Y., Wang, J., Mishra, A., Joseph, J., Berry, J. E., McGee, S., Lee, E., Sun, H., Wang, J., Jin, T., Zhang, H., Dai, J., Krebsbach, P. H., Keller, E. T., Pienta, K. J., & Taichman, R. S. (2013). Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis. Nature communications, 4, Article 1795. https://doi.org/10.1038/ncomms2766

@article{ec90e17d67d74dc9afcdea76a2d16eb5,

title = "Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis",

abstract = "Tumours recruit mesenchymal stem cells to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that CXCL16, a ligand for CXCR6, facilitates mesenchymal stem cell or very small embryonic-like cells recruitment into prostate tumours. CXCR6 signalling stimulates the conversion of mesenchymal stem cells into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also known as CXCL12. CXCL12 expressed by cancer-associated fibroblasts then binds to CXCR4 on tumour cells and induces an epithelial-to-mesenchymal transition, which ultimately promotes metastasis to secondary tumour sites. Our results provide the molecular basis for mesenchymal stem cell recruitment into tumours and how this process leads to tumour metastasis.",

author = "Younghun Jung and Kim, {Jin Koo} and Yusuke Shiozawa and Jingcheng Wang and Anjali Mishra and Jeena Joseph and Berry, {Janice E.} and Samantha McGee and Eunsohl Lee and Hongli Sun and Jianhua Wang and Taocong Jin and Honglai Zhang and Jinlu Dai and Krebsbach, {Paul H.} and Keller, {Evan T.} and Pienta, {Kenneth J.} and Taichman, {Russell S.}",

note = "Funding Information: This work is directly supported by the National Institutes of Health (CA163124, CA093900, CA166307, CA069568, DK082481, MH095589, Y.S., E.T.K. P.H.K, K.J.P. and R.S.T.), the Fund for Cancer Research (R.S.T.), the Department of Defense (E.T.K., Y.S. and R.S.T.), the Prostate Cancer Foundation (Y.S, K.J.P. and R.S.T.), National Natural Funding of China (81071747) (Jianhua Wang), National Key Program (973) for Basic Research of China (2011CB510106) (Jianhua Wang) and Shanghai Pujiang Program (10PJ1406400) (Jianhua Wang). Logistical support was also received from the University of Michigan FACS and Imaging Cores, and the Dental School{\textquoteright}s Molecular Biology Core.",

year = "2013",

doi = "10.1038/ncomms2766",

language = "English (US)",

volume = "4",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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T1 - Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis

AU - Jung, Younghun

AU - Kim, Jin Koo

AU - Shiozawa, Yusuke

AU - Wang, Jingcheng

AU - Mishra, Anjali

AU - Joseph, Jeena

AU - Berry, Janice E.

AU - McGee, Samantha

AU - Lee, Eunsohl

AU - Sun, Hongli

AU - Wang, Jianhua

AU - Jin, Taocong

AU - Zhang, Honglai

AU - Dai, Jinlu

AU - Krebsbach, Paul H.

AU - Keller, Evan T.

AU - Pienta, Kenneth J.

AU - Taichman, Russell S.

N1 - Funding Information: This work is directly supported by the National Institutes of Health (CA163124, CA093900, CA166307, CA069568, DK082481, MH095589, Y.S., E.T.K. P.H.K, K.J.P. and R.S.T.), the Fund for Cancer Research (R.S.T.), the Department of Defense (E.T.K., Y.S. and R.S.T.), the Prostate Cancer Foundation (Y.S, K.J.P. and R.S.T.), National Natural Funding of China (81071747) (Jianhua Wang), National Key Program (973) for Basic Research of China (2011CB510106) (Jianhua Wang) and Shanghai Pujiang Program (10PJ1406400) (Jianhua Wang). Logistical support was also received from the University of Michigan FACS and Imaging Cores, and the Dental School’s Molecular Biology Core.

PY - 2013

Y1 - 2013

N2 - Tumours recruit mesenchymal stem cells to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that CXCL16, a ligand for CXCR6, facilitates mesenchymal stem cell or very small embryonic-like cells recruitment into prostate tumours. CXCR6 signalling stimulates the conversion of mesenchymal stem cells into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also known as CXCL12. CXCL12 expressed by cancer-associated fibroblasts then binds to CXCR4 on tumour cells and induces an epithelial-to-mesenchymal transition, which ultimately promotes metastasis to secondary tumour sites. Our results provide the molecular basis for mesenchymal stem cell recruitment into tumours and how this process leads to tumour metastasis.

AB - Tumours recruit mesenchymal stem cells to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that CXCL16, a ligand for CXCR6, facilitates mesenchymal stem cell or very small embryonic-like cells recruitment into prostate tumours. CXCR6 signalling stimulates the conversion of mesenchymal stem cells into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also known as CXCL12. CXCL12 expressed by cancer-associated fibroblasts then binds to CXCR4 on tumour cells and induces an epithelial-to-mesenchymal transition, which ultimately promotes metastasis to secondary tumour sites. Our results provide the molecular basis for mesenchymal stem cell recruitment into tumours and how this process leads to tumour metastasis.

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Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis

Abstract

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