Primary breast cancer stem-like cells metastasise to bone, switch phenotype and acquire a bone tropism signature.
Br J Cancer
; 108(12): 2525-36, 2013 Jun 25.
Article
em En
| MEDLINE
| ID: mdl-23801032
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 CD44âºCD24â» 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 CD44â»CD24⺠and showed tumorigenic abilities after injection in secondary mice. CD44â»CD24⺠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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
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Osso e Ossos
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Neoplasias Ósseas
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Neoplasias da Mama
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Carcinoma
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Transcriptoma
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Animals
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Female
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Humans
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Itália