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Mesenchymal stem cells within tumour stroma promote breast cancer metastasis

Author

Listed:
  • Antoine E. Karnoub

    (Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA)

  • Ajeeta B. Dash

    (Genzyme Corporation, Framingham, Massachusetts 01701, USA)

  • Annie P. Vo

    (Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA)

  • Andrew Sullivan

    (Genzyme Corporation, Framingham, Massachusetts 01701, USA)

  • Mary W. Brooks

    (Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA)

  • George W. Bell

    (Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA)

  • Andrea L. Richardson

    (Brigham and Women’s Hospital, Boston, Massachusetts 02115, USA)

  • Kornelia Polyak

    (Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Ross Tubo

    (Genzyme Corporation, Framingham, Massachusetts 01701, USA)

  • Robert A. Weinberg

    (Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA)

Abstract

Mesenchymal stem cells have been recently described to localize to breast carcinomas, where they integrate into the tumour-associated stroma. However, the involvement of mesenchymal stem cells (or their derivatives) in tumour pathophysiology has not been addressed. Here, we demonstrate that bone-marrow-derived human mesenchymal stem cells, when mixed with otherwise weakly metastatic human breast carcinoma cells, cause the cancer cells to increase their metastatic potency greatly when this cell mixture is introduced into a subcutaneous site and allowed to form a tumour xenograft. The breast cancer cells stimulate de novo secretion of the chemokine CCL5 (also called RANTES) from mesenchymal stem cells, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. This enhanced metastatic ability is reversible and is dependent on CCL5 signalling through the chemokine receptor CCR5. Collectively, these data demonstrate that the tumour microenvironment facilitates metastatic spread by eliciting reversible changes in the phenotype of cancer cells.

Suggested Citation

  • Antoine E. Karnoub & Ajeeta B. Dash & Annie P. Vo & Andrew Sullivan & Mary W. Brooks & George W. Bell & Andrea L. Richardson & Kornelia Polyak & Ross Tubo & Robert A. Weinberg, 2007. "Mesenchymal stem cells within tumour stroma promote breast cancer metastasis," Nature, Nature, vol. 449(7162), pages 557-563, October.
    • Handle: RePEc:nat:nature:v:449:y:2007:i:7162:d:10.1038_nature06188
    DOI: 10.1038/nature06188
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    Cited by:

    1. Lena Cords & Sandra Tietscher & Tobias Anzeneder & Claus Langwieder & Martin Rees & Natalie Souza & Bernd Bodenmiller, 2023. "Cancer-associated fibroblast classification in single-cell and spatial proteomics data," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Urban Lendahl & Lars Muhl & Christer Betsholtz, 2022. "Identification, discrimination and heterogeneity of fibroblasts," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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