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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 15, 2024 |
| Title |
Natural killer cell regulation of breast cancer stem cells mediates metastatic dormancy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Breast cancer patients with estrogen receptor positive tumors face a constant risk of disease recurrence for the remainder of their lives. Dormant tumor cells residing in tissues such as the bone marrow may generate clinically significant metastases many years after initial diagnosis. Previous studies suggest that dormant cells display “stem like” properties (CSCs), which may be regulated by the immune system. Although many studies have examined tumor cell intrinsic characteristics of dormancy, the role of the immune system in controlling dormancy and its escape is not well understood. This scientific gap is due, in part, to a lack of immunocompetent mouse models of breast cancer dormancy with many studies involving human xenografts in immunodeficient mice. To overcome this limitation, we studied dormancy in immunocompetent, syngeneic mouse breast cancer models. We find that PyMT, Met-1 and D2.0R cell lines contain CSCs that display both short- and long-term metastatic dormancy in vivo, which is dependent on the host immune system. Natural killer cells were key for the metastatic dormancy phenotype observed for D2.0R and the role of NK cells in regulating CSCs was further investigated. Quiescent D2.0R CSC are resistant to NK cytotoxicity, while proliferative D2.0R CSC were sensitive to NK cytotoxicity both in vitro and in vivo. This resistance was mediated, in part, by the expression of Bach1 and Sox2 transcription factors. NK killing was enhanced by the STING agonist MSA-2. Collectively, our findings demonstrate the important role of immune regulation of breast tumor dormancy and highlight the importance of utilizing immunocompetent models to study this phenomenon.
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| Overall design |
D2.0R tumor cells were labeled with celltrace far red and cultured for one week in 2% FBS DMEM media. After a week of culture CTFR+ label retaining cells (quiescent) and CTFR- non-label retaining cells (proliferative) were FACS sorted.
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| Contributor(s) |
Bushnell GG, Wicha M |
| Citation(s) |
37873211 |
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| Submission date |
May 15, 2024 |
| Last update date |
May 15, 2024 |
| Contact name |
Grace Bushnell |
| E-mail(s) |
ggb@umich.edu
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| Organization name |
University of Michigan
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| Department |
Internal Medicine
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| Lab |
Wicha Lab
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| Street address |
2800 Plymouth Rd NCRC B26
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| City |
Ann Arbor |
| State/province |
MI |
| ZIP/Postal code |
48109 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA1111891 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE267583_gene_expected_count.annot.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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