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Status |
Public on Mar 16, 2023 |
Title |
Type I Interferon Response in Astrocytes Promotes Brain Metastasis by Enhancing Monocytic Myeloid Cell Recruitment |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Cancer metastasis to the brain is a significant clinical problem. Metastasis is the consequence of favorable interactions between invaded cancer cells and the microenvironment. Here, we demonstrate that cancer-activated astrocytes create a sustained low-level activated type I interferon (IFN) microenvironment in brain metastatic lesions. We further confirm that the IFN response in astrocytes facilitate brain metastasis. Mechanistically, IFN signaling in astrocytes activates C-C Motif Chemokine Ligand 2 (CCL2) production, which further increases the recruitment of monocytic myeloid cells. The correlation between CCL2 and monocytic myeloid cells is confirmed in clinical brain metastasis samples. Lastly, genetically or pharmacologically inhibiting C-C Motif Chemokine Receptor 2 (CCR2) significantly reduces brain metastases. Our study clarifies a pro-metastatic effect of type I IFN in the brain even though IFN response has been considered to have anti-tumor effects. Moreover, this work expands our understandings on the interactions between cancer-activated astrocytes and immune cells in brain metastasis.
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Overall design |
RNA seq in astrocytes and MDA231 tumor cells alone or cocultured
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Contributor(s) |
Ma W, Chen Q |
Citation(s) |
37149684 |
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Submission date |
Feb 01, 2023 |
Last update date |
Aug 04, 2023 |
Contact name |
Priyankara J Wickramasinghe |
E-mail(s) |
priyaw@wistar.org
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Phone |
2154956837
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Organization name |
The Wistar Institute
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Department |
Bioinformatics
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Lab |
Genomics
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Street address |
3601 Spruce Street
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City |
Philadelphia |
State/province |
PA |
ZIP/Postal code |
19104 |
Country |
USA |
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Platforms (1) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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Samples (8)
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Relations |
BioProject |
PRJNA930486 |