Omics · study · 2026
Mesothelin-induced lysosomal biogenesis sustains neutrophil longevity to drive brain metastasis
Listed in NCBI GEO
Tumor-associated neutrophil (TAN) enrichment is a defining feature and driving force of brain metastases (BrM), a leading cause of death in solid tumors.
Description
Yet, the mechanisms governing TAN enrichment in BrM remains undefined. Herein, we demonstrate that BrM cell-derived shed soluble mesothelin (sMSLN) is critical for prolonging neutrophil survival to facilitate tumor cell colonization and outgrowth in the brain.
Specifically, sMSLN binds specifically to toll-like receptor 4 (TLR4) on neutrophil to activate the JAK2-STAT3 pathway. This activation promotes lysosomal biogenesis and function, reducing cellular reactive oxygen species (ROS) and inhibiting neutrophil apoptosis. Depletion of neutrophil or blockade of the TLR4-STAT3 pathway abrogates sMSLN-induced BrM progression.
Read the rest (1 more)
Targeting MSLN with Anetumab effectively reduces TAN enrichment, and combining this with TLR4 inhibition synergistically suppresses lung cancer BrM. Our findings establish a critical role for tumor cell-derived sMSLN in sustaining neutrophil longevity and driving BrM, highlighting the MSLN-TLR4 axis as a promising therapeutic target for brain metastatic tumors.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE346nnn/GSE346524 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE346524 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1525702 ncbi.nlm.nih.gov/bioproject/PRJNA1525702 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE346524 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |