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 and Russell S. Taichman ()
Additional contact information
Younghun Jung: University of Michigan School of Dentistry
Jin Koo Kim: University of Michigan School of Dentistry
Yusuke Shiozawa: University of Michigan School of Dentistry
Jingcheng Wang: University of Michigan School of Dentistry
Anjali Mishra: University of Michigan School of Dentistry
Jeena Joseph: University of Michigan School of Dentistry
Janice E. Berry: University of Michigan School of Dentistry
Samantha McGee: University of Michigan School of Dentistry
Eunsohl Lee: University of Michigan School of Dentistry
Hongli Sun: University of Michigan School of Dentistry
Jianhua Wang: Institute of Medical Sciences, Shanghai Jiao-Tong University School of Medicine
Taocong Jin: Restorative Sciences and Endodontics, University of Michigan School of Dentistry
Honglai Zhang: University of Michigan Medical School
Jinlu Dai: University of Michigan Medical School
Paul H. Krebsbach: University of Michigan School of Dentistry
Evan T. Keller: University of Michigan Medical School
Kenneth J. Pienta: University of Michigan Medical School
Russell S. Taichman: University of Michigan School of Dentistry

Nature Communications, 2013, vol. 4, issue 1, 1-11

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms2766

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