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Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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, 2013. "Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis," Nature Communications, Nature, vol. 4(1), pages 1-11, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2766
    DOI: 10.1038/ncomms2766
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    Cited by:

    1. Feng Wang & Yunxuan Li & Zhaona Yang & Wenbin Cao & Ying Liu & Luyao Zhao & Tingting Zhang & Chenxi Zhao & Jinmei Yu & Jiaojiao Yu & Jichao Zhou & Xiaowei Zhang & Ping-Ping Li & Mingzhe Han & Sizhou F, 2024. "Targeting IL-17A enhances imatinib efficacy in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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