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A convenient clinically relevant model of human breast cancer bone metastasis

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Abstract

Breast cancer patients with advanced disease exhibit bone metastases, leading to the formation of osteolytic lesions for which the only currently available treatments are palliative. Here, we describe how we refined a mouse model of human breast cancer metastasis into bone, characterized its transcriptome and demonstrated its clinical relevance. Cells were selected from bone metastases caused by MDA-MB-231 cells after several in vivo passages, and engineered to express luciferase. Whole body bioluminescence live imaging indicated that the selected isogenic B02 clone was unique in its ability to form rapidly growing osteolytic bone metastases. B02 cells were detected as early as 10 days after tail vein injection, as opposed to 1 month after cardiac injection in other haematogenous models. Whole transcriptomic analysis identified 114 upregulated and 247 downregulated genes in B02 cells compared to the parental cells, several of which represent novel targets. In addition, there was a 50% overlap between the B02 signature and a recently described signature obtained from human breast cancer bone metastases. Consistent with the plasticity of an aggressive metastatic variant, 10% of the regulated genes are involved in proliferation, migration, invasion and angiogenesis. Strikingly, B02 cells also express osteoblast-specific genes, thus mimicking a process referred to as osteomimicry in the clinic. The B02 cells “human bone metastatic signature”, the expression of bone-specific genes, as well as the live imaging of this convenient model highlight its clinical relevance and usefulness during drug development.

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Acknowledgment

This work was partially supported by a grant from the European Community contract No. LSHCCT2004-506049. www.metabre.org

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Authors and Affiliations

  1. Galapagos SASU, 102 route de Noisy, Romainville, 93230, France

    Teresa Garcia, Philippe Clément-Lacroix & Philippe Pujuguet

  2. Imperial College London, South Kensington Campus, 532, Sir Alexander Fleming Building, London, UK

    Amanda Jackson

  3. Unit Research U664, Laennec School of Medicine, Inserm, rue Guillaume Paradin, Lyon cedex 08, 69372, France

    Richard Bachelier & Philippe Clézardin

  4. Department of Cell Biology, Yale University, New Heaven, CT, USA

    Roland Baron

Authors
  1. Teresa Garcia
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  2. Amanda Jackson
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  3. Richard Bachelier
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  4. Philippe Clément-Lacroix
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  5. Roland Baron
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  6. Philippe Clézardin
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  7. Philippe Pujuguet
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Correspondence to Philippe Pujuguet.

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Garcia, T., Jackson, A., Bachelier, R. et al. A convenient clinically relevant model of human breast cancer bone metastasis. Clin Exp Metastasis 25, 33–42 (2008). https://doi.org/10.1007/s10585-007-9099-1

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  • DOI: https://doi.org/10.1007/s10585-007-9099-1

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