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Series GSE204922 Query DataSets for GSE204922
Status Public on Dec 31, 2022
Title The Kupffer cell-specifying factor Id3 endows macrophages with antimetastatic activity
Organism Mus musculus
Experiment type Other
Summary The anti-tumor activity of macrophages is mediated in part via phagocytosis and controlled by a balance between the recognition of live cells by activating receptors and inhibitory receptors. The latter protects host tissues during infection but allows tumoral cells to escape phagocytosis and promotes metastasis. We investigated the mechanisms that control anti-metastatic activity of macrophages and found that the transcriptional repressor and Kupffer cells (KC)-specifying factor ID3 is required and sufficient to orchestrate tumor cell killing by macrophages in vivo and in vitro and reduces by ~50% liver and lung colonization by metastatic-initiating cells invading from the portal vein in long-term orthotopic pancreatic cancer models. Loss-of-function and gain -of functions experiments indicate that ID3 controls expression of activating and inhibitory receptors, in particular the inhibitory receptor SIRPα, which boost their phagocytic activity against tumor cells. Mechanistically, ID3 prevents binding of ELK1 and the E-Box factor E2A to promoter/enhancer regions of the inhibitory receptor Sirpα gene, which limits expression of SIRPα at levels compatible with efficient phagocytosis of tumor cells and prevents its upregulation by inflammatory stimuli. This mechanism endows macrophages with anti-metastatic activity.
 
Overall design KPC-1 tumor cells DNA profiles from R26LSL-DTR and Clec4fCre;R26LSL-DTR mice. DNA samples were extracted with QIAamp DNA Micro Kit, DNA were used for library construction using the KAPA Hyper Prep Kit (Kapa Biosystems KK8504) with 8 cycles of PCR. After sample barcoding, 100-110ng of each library were pooled and captured by hybridization with the mm_IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets) assay.
 
Contributor(s) Deng Z, Fragkogianni S, Geissmann F
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Submission date May 26, 2022
Last update date Dec 31, 2022
Contact name Bic MSKCC
Organization name Memorial SLoan-Kettering Cancer Center
Street address 1275 York Ave.
City New York
State/province NY
ZIP/Postal code 10021
Country USA
 
Platforms (1)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (13)
GSM6202393 IMPACT_KPC KC_WT rep1
GSM6202394 IMPACT_KPC KC_WT rep2
GSM6202395 IMPACT_KPC KC_WT rep3
Relations
BioProject PRJNA842726

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Supplementary file Size Download File type/resource
GSE204922_IMPACT.xlsx 54.6 Kb (ftp)(http) XLSX
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Processed data are available on Series record

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