期刊
BRITISH JOURNAL OF CANCER
卷 108, 期 12, 页码 2525-2536出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2013.271
关键词
bone metastasis; breast cancer; cancer stem cell; human-in-mice model; osteotropism
类别
资金
- Compagnia di San Paolo
- Italian Ministry of Health: Ricerca Sanitaria Finalizzata e Giovani Ricercatori [GR 2009-1584485]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据