Primary breast cancer stem-like cells metastasise to bone, switch phenotype and acquire a bone tropism signature

L. D'Amico, S. Patanè, C. Grange, B. Bussolati, C. Isella, L. Fontani, L. Godio, M. Cilli, P. D'Amelio, G. Isaia, E. Medico, R. Ferracini, I. Roato

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Bone metastases represent a common and severe complication in breast cancer, and the involvement of cancer stem cells (CSCs) in the promotion of bone metastasis is currently under discussion. Here, we used a human-in-mice model to study bone metastasis formation due to primary breast CSCs-like colonisation. Methods: Primary CD44+CD24- breast CSCs-like were transduced by a luciferase-lentiviral vector and injected through subcutaneous and intracardiac (IC) routes in non-obese/severe-combined immunodeficient (NOD/SCID) mice carrying subcutaneous human bone implants. The CSCs-like localisation was monitored by in vivo luciferase imaging. Bone metastatic CSCs-like were analysed through immunohistochemistry and flow cytometry, and gene expression analyses were performed by microarray techniques. Results: Breast CSCs-like colonised the human-implanted bone, resulting in bone remodelling. Bone metastatic lesions were histologically apparent by tumour cell expression of epithelial markers and vimentin. The bone-isolated CSCs-like were CD44+ CD24- and showed tumorigenic abilities after injection in secondary mice. CD44+CD24- CSCs-like displayed a distinct bone tropism signature that was enriched in genes that discriminate bone metastases of breast cancer from metastases at other organs. Conclusion: Breast CSCs-like promote bone metastasis and display a CSCs-like bone tropism signature. This signature has clinical prognostic relevance, because it efficiently discriminates osteotropic breast cancers from tumour metastases at other sites.

Original languageEnglish
Pages (from-to)2525-2536
Number of pages12
JournalBritish Journal of Cancer
Volume108
Issue number12
DOIs
Publication statusPublished - Jun 25 2013

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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