Primary breast cancer stem-like cells metastasise to bone, switch phenotype and acquire a bone tropism signature.
Details
Serval ID
serval:BIB_E906D39C3E51
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Primary breast cancer stem-like cells metastasise to bone, switch phenotype and acquire a bone tropism signature.
Journal
British journal of cancer
ISSN
1532-1827 (Electronic)
ISSN-L
0007-0920
Publication state
Published
Issued date
25/06/2013
Peer-reviewed
Oui
Volume
108
Number
12
Pages
2525-2536
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
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.
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.
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.
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.
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.
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.
Keywords
Adult, Animals, Bone Neoplasms/genetics, Bone Neoplasms/secondary, Bone and Bones/metabolism, Bone and Bones/pathology, Breast Neoplasms/genetics, Breast Neoplasms/pathology, Carcinoma/genetics, Carcinoma/pathology, Female, Gene Expression Regulation, Neoplastic, Genes, Switch/genetics, Humans, Mice, Mice, Inbred NOD, Mice, SCID, Neoplastic Stem Cells/metabolism, Neoplastic Stem Cells/pathology, Organ Specificity/genetics, Phenotype, Transcriptome/physiology
Pubmed
Web of science
Open Access
Yes
Create date
14/01/2020 9:00
Last modification date
15/01/2020 7:26