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Series GSE261138 Query DataSets for GSE261138
Status Public on Jun 26, 2024
Title Cancer EVP Uptake in Lung Interstitial Macrophages Enhances Vascular Permeability and Metastatic Potential (in vivo)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
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 ITGα5 compared to breast tumors, and knock down ofintegrin-α5impairs 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.
 
Overall design To evaluate the effect of B16F10 on interstitial machrophages (IMs), we sorted IMs which uptaken labled EVPs and control IMs. We then performed gene expression profilling anaylsis.
 
Contributor(s) Dror S, Lyden D
Citation(s) 38853850
Submission date Mar 07, 2024
Last update date Jun 26, 2024
Contact name David Lyden
Organization name Weill Cornell medical College
Department Pediatrics
Lab Lyden lab
Street address 413 East 69th Street, Room BB1228
City new york
State/province NY
ZIP/Postal code 10021
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (6)
GSM8135726 IMs ,B16F10 EVP, in vivo, rep1
GSM8135727 IMs ,B16F10 EVP, in vivo, rep2
GSM8135728 IMs .B16F10 EVP, in vivo, rep3
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
Relations
BioProject PRJNA1085348

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE261138_details_counts.xlsx 4.3 Mb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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