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| Status |
Public on Nov 30, 2013 |
| Title |
Cancer stem cells from lobular infiltrating breast tumor metastasize to bone and acquire a gene signature associated to bone tropism |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
We investigated the role of breast cancer stem-like cells (CSCs-like), isolated from primary tumor, in promoting bone metastases in a human-in-mice model. Luciferase-transduced CD44+CD24- breast CSCs-like were injected through subcutaneous (SC) and intracardiac (IC) route in nonobese/severe combined immunodeficient (NOD/SCID) mice carrying subcutaneous human bone implants. The implanted bone was viable, active and human neo-vascularization was present. By in vivo luciferase imaging, we monitored tumor growth and detected bone-localized breast CSCs-like, both after SC and IC injection. Bone metastatic lesions were histologically evident, and tumor cells expressed epithelial markers and vimentin. Bone metastatic cells isolated from bone implants showed a CD44-CD24+ phenotype and re-created tumors and bone metastases after injection in secondary mice. A “bone tropism” expression signature was found to distinguish bone-colonizing cells from parental CSCs-like and to persist at subsequent passages also in the absence of surrounding bone tissue. The bone tropism signature displayed significant enrichment in genes discriminating bone metastases of breast cancer from metastases at other organs. Our results demonstrate the ability of breast CSCs-like to promote bone metastasis and provide a CSCs-like bone tropism signature, with potential prognostic value.
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| Overall design |
C10 breast cancer stem-like cells (CSCs-like) were derived as mammospheres from a lobular-infiltrating breast carcinoma (ER+, HER2-). Samples are organized in the following groups: (i) Breast CSCs-like (C10, duplicate); (ii) Luciferase-transduced CSCs-like (C10L, simplicate); (iii) Bone-isolated C10L metastatic cells (C10-bone, duplicate) and subsequently (iv) grown in vitro as spheroids (C10-CSC, simplicate) or (v) re-grown in subcutaneous implants (C10-SC, duplicate).
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| Contributor(s) |
Medico E, Isella C, Roato I |
| Citation missing |
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| Submission date |
Feb 27, 2012 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Enzo Medico |
| E-mail(s) |
enzo.medico@ircc.it
|
| Phone |
+39-011-9933234
|
| Organization name |
Candiolo Cancer Institute, University of Torino
|
| Department |
Oncology
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| Lab |
Laboratory of Oncogenomics
|
| Street address |
Strada Prov. 142, km 3,95
|
| City |
Candiolo |
| State/province |
TO |
| ZIP/Postal code |
10060 |
| Country |
Italy |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA152975 |
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