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- Title
Primary breast cancer stem-like cells metastasise to bone, switch phenotype and acquire a bone tropism signature.
- Authors
D Amico, L; Patanè, S; Grange, C; Bussolati, B; Isella, C; Fontani, L; Godio, L; Cilli, M; D Amelio, P; Isaia, G; Medico, E; Ferracini, R; Roato, I
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Publication
British Journal of Cancer, 2013, Vol 108, Issue 12, p2525
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/bjc.2013.271