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GEO help: Mouse over screen elements for information. |
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Status |
Public on Jun 26, 2024 |
Title |
Cancer EVP Uptake in Lung Interstitial Macrophages Enhances Vascular Permeability and Metastatic Potential (in vitro) |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Enhanced vascular permeability in the pre-metastatic niche facilitates tumor cell extravasation and metastasis. Extracellular vesicles and particles (EVPs) are pivotal mediators of cancer progression, including induction of vascular permeability. We identify a novel mechanism whereby melanoma and osteosarcoma EVPs (B16F10 and K7M2) enhance endothelial cell permeability, tumor extravasation and lung metastasis.In contrast, EVPs from breast tumors (4T1 and 67NR) elicited only mild vascular permeability, tumor cell extravasation, and metastasis. EVP induced vascular leakiness is observed within 48h following tumor implantation and as early one hour following direct injection of the B16F10 or K7M2 derived EVPs in non-tumor bearing mice. Rather than acting directly on endothelial cells, EVPs activated interstitial macrophages (IMs) anddepletion of IM with a CSF1R antibody significantly reduced vascular leakiness and metastatic potential.Subsequent activation of JAK/STAT signaling in IMs induces IL-6 secretion which in turn induces endothelial permeability.B16F10 and K7M2 EVPs highly expressed integrin-α5 compared to breast tumors, and knock down ofITGα5impairs IM signaling, vascular permeability and metastasis. Furthermore, in patients Il-6 expression is elevated in tumor-adjacent IMs compared to distant tissues. Our findings identify a key role for IMs in mediating tumor type-specific EVP-driven vascular permeability and metastasis, offering promising targets for therapeutic intervention.
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Overall design |
To evaluate the effect of ITGA5 IN EVPs on interstitial machrophages (IMs), we sorted IMs from naïve mice, and treat them with EVPs from B16F10 CON KO, B16G10 ITGA5 KO, K7M2 CON KO and K7M2 ITGA5 KO cell line.. We then performed gene expression profilling anaylsis.
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Contributor(s) |
Dror S, Lyden D |
Citation(s) |
38853850 |
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Submission date |
Mar 07, 2024 |
Last update date |
Jun 26, 2024 |
Contact name |
David Lyden |
Organization name |
Weill Cornell medical College
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Department |
Pediatrics
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Lab |
Lyden lab
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Street address |
413 East 69th Street, Room BB1228
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City |
new york |
State/province |
NY |
ZIP/Postal code |
10021 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (10)
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GSM8135719 |
IMs ,B16F10 ITGA5 KO EVP, rep2 |
GSM8135720 |
IMs ,K7M2 CON KO EVP, rep1 |
GSM8135721 |
IMs ,K7M2 CON KO EVP, rep2 |
GSM8135722 |
IMs ,K7M2 ITGA5 KO EVP, rep1 |
GSM8135723 |
IMs ,K7M2 ITGA5 KO EVP, rep2 |
GSM8135724 |
IMs .control, rep1 |
GSM8135725 |
IMs .control, rep2 |
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This SubSeries is part of SuperSeries: |
GSE261139 |
Tumour-derived Extracellular Vesicle and Particle Reprogramming of Interstitial Macrophages in the Lung Pre-Metastatic Niche Enhances Vascular Permeability and Metastatic Potential |
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Relations |
BioProject |
PRJNA1085337 |
Supplementary file |
Size |
Download |
File type/resource |
GSE261137_details_counts.xlsx |
7.0 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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