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 journalArticle

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 languageEnglish (US)
Article number1795
JournalNature communications
Volume4
DOIs
StatePublished - May 20 2013
Externally publishedYes

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ASJC Scopus subject areas

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

Cite this

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, [1795]. https://doi.org/10.1038/ncomms2766