ArticleNeuro-oncology2024
Invasive growth of brain metastases is linked to CHI3L1 release from pSTAT3-positive astrocytes.
Article in Neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 18 citations in OpenAlex.
- Advances in the role of astrocytes in glioma progression and therapy.Acta pharmacologica Sinica · 2026Review
- Lung Cancer Brain Metastasis: Brain Microenvironmental Adaptation, Therapeutic Resistance and Translational Strategies.Cancer science · 2026Review
- Brain metastasis-associated fibroblasts shape the tumour microenvironment to enhance cancer cell invasion.Brain pathology (Zurich, Switzerland) · 2026Article
- The Origin of Cancer-Associated Fibroblasts (CAFs) in Brain Metastases: Seven Hypotheses and Current Evidence.Cancers · 2026Review
- S100A14 in Tumor-Derived EVs Targets PIAS3 to Reprogram Astrocytes and Induce Immunosuppressive Microenvironment Promoting Brain Metastasis and Germacrone Reversal Effect.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Effect of the miR‑26a/b‑5p‑STAT3‑YKL‑40 regulatory axis on proliferation, migration, and invasion of endometrial cancer cells.Oncology reports · 2026Article
- Distinct immune landscapes characterize highly versus minimally invasive brain metastases.JCI insight · 2026Article
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- CHI3L1: a novel regulator of vascular remodeling in pulmonary arterial hypertension.Molecular and cellular biochemistry · 2026Article
- Astrocyte-driven immunosuppression in the brain tumor microenvironment.Nature immunology · 2026Review
- CHI3L1 Is Associated With TP53 Signaling and Promotes Papillary Thyroid Carcinoma Progression.Cancer reports (Hoboken, N.J.) · 2026Article
- The evolving landscape of brain metastasis: volume II.Trends in cancer · 2026Review
- Toward functional precision oncology: organotypic brain slices in glioblastoma.Frontiers in oncology · 2026Review
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- STAT3 expression in brain metastases from breast cancer is correlated with molecular subtype and impacts clinical outcome.Neuro-oncology · 2025Article
- Decoding the mechanisms underlying breast cancer brain metastasis: paving the way for precision therapeutics.Biomarker research · 2025Review
- Peritumoral and intratumoral magnetic resonance imaging-based radiomics of brain metastases for predicting the response to EGFR-tyrosine kinase inhibitors in metastatic non-small cell lung cancer.Quantitative imaging in medicine and surgery · 2025Article
- Astrocyte involvement in brain metastasis: from biological mechanisms to therapeutic strategies.Cancer metastasis reviews · 2025Review
- Complex I inhibition combined with TLR activation in the breast tumor microenvironment educates cytotoxic neutrophils.Science advances · 2025Article
- The Role of Extracellular Vesicles in the Control of Vascular Checkpoints for Cancer Metastasis.Cancers · 2025Review
Corrections and comments
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Authors and funding
25 authors at 8 institutions in 3 countries.
Funding
Abstract
backgroundCompared to minimally invasive brain metastases (MI BrM), highly invasive (HI) lesions form abundant contacts with cells in the peritumoral brain parenchyma and are associated with poor prognosis. Reactive astrocytes (RAs) labeled by phosphorylated STAT3 (pSTAT3) have recently emerged as a promising therapeutic target for BrM. Here, we explore whether the BrM invasion pattern is influenced by pSTAT3+ RAs and may serve as a predictive biomarker for STAT3 inhibition.
methodsWe used immunohistochemistry to identify pSTAT3+ RAs in HI and MI human and patient-derived xenograft (PDX) BrM. Using PDX, syngeneic, and transgenic mouse models of HI and MI BrM, we assessed how pharmacological STAT3 inhibition or RA-specific STAT3 genetic ablation affected BrM growth in vivo. Cancer cell invasion was modeled in vitro using a brain slice-tumor co-culture assay. We performed single-cell RNA sequencing of human BrM and adjacent brain tissue.
resultsRAs expressing pSTAT3 are situated at the brain-tumor interface and drive BrM invasive growth. HI BrM invasion pattern was associated with delayed growth in the context of STAT3 inhibition or genetic ablation. We demonstrate that pSTAT3+ RAs secrete Chitinase 3-like-1 (CHI3L1), which is a known STAT3 transcriptional target. Furthermore, single-cell RNA sequencing identified CHI3L1-expressing RAs in human HI BrM. STAT3 activation, or recombinant CHI3L1 alone, induced cancer cell invasion into the brain parenchyma using a brain slice-tumor plug co-culture assay.
conclusionsTogether, these data reveal that pSTAT3+ RA-derived CHI3L1 is associated with BrM invasion, implicating STAT3 and CHI3L1 as clinically relevant therapeutic targets for the treatment of HI BrM.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.