ArticleCell2017
Complement Component 3 Adapts the Cerebrospinal Fluid for Leptomeningeal Metastasis.
Article in Cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 221 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
221 citing papers in PubMed, 2 syntheses or guidelines pooled it, 354 citations in OpenAlex.
- Pooled it
- A systematic review of craniospinal irradiation for leptomeningeal disease: past, present, and future.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Pooled it
- Preclinical evaluation of trastuzumab deruxtecan in a new HER2+ leptomeningeal colonization model.Cancer letters · 2026Article
- The role of radiation therapy in leptomeningeal disease from breast cancer - a multicenter analysis.Clinical and translational radiation oncology · 2026Article
- Article
- Lung Cancer Brain Metastasis: Brain Microenvironmental Adaptation, Therapeutic Resistance and Translational Strategies.Cancer science · 2026Review
- Liver-derived complement component 3 promotes the susceptibility to stress-induced depression by impairing blood-brain barrier integrity.Molecular psychiatry · 2026Article
- Intrathecal nivolumab in metastatic solid tumors with leptomeningeal disease: dose escalation part of the multicenter IT-PD1/NOA-26 phase 1 trial.Nature cancer · 2026Article
- Evaluation of cerebrospinal fluid human epididymis protein 4 for leptomeningeal metastasis in non-small cell lung cancer: a prospective cohort study.BMC cancer · 2026Article
- Role of CSF interleukin-6 in the prognosis of patients with Leptomeningeal metastases of glioblastoma.Discover oncology · 2026Article
- Cerebrospinal Fluid in Pediatric Neuro-Oncology: Molecular Diagnosis, Disease Monitoring, and Clinical Translation.International journal of molecular sciences · 2026Review
- Region-specific proteomic profiling of brain interstitial fluidLab on a chip · 2026Article
- A tumor-derived metabolite primes the leptomeningeal pre-metastatic niche.Nature cancer · 2026Article
- Leptomeningeal metastatic cancer cells induce a permissive choroid plexus vasculature through extracellular-vesicle-derived 5-HIAA signaling.Nature cancer · 2026Article
- Meningeal immune convergence: IFN-γ-driven DC-NK axis suppresses leptomeningeal tumor.Journal of the National Cancer Center · 2026Article
- Melanoma leptomeningeal disease: Advances in diagnosis and emerging therapeutic strategies.World journal of experimental medicine · 2026Review
- Fluid shear stress activates a targetable mechano-metastatic cascade to promote medulloblastoma metastasis.Nature biomedical engineering · 2026Article
- The evolving landscape of brain metastasis: volume II.Trends in cancer · 2026Review
- Inhibiting Liver-Derived C3 Protein Rescues Anesthesia/Surgery-Induced Cognitive Impairment, Synaptic Disorders, and Microglial Phagocytosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The immune microenvironment of the central nervous system and neuromodulation: new perspectives in lung cancer brain metastases research.Frontiers in immunology · 2026Review
161 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
We molecularly dissected leptomeningeal metastasis, or spread of cancer to the cerebrospinal fluid (CSF), which is a frequent and fatal condition mediated by unknown mechanisms. We selected lung and breast cancer cell lines for the ability to infiltrate and grow in CSF, a remarkably acellular, mitogen-poor metastasis microenvironment. Complement component 3 (C3) was upregulated in four leptomeningeal metastatic models and proved necessary for cancer growth within the leptomeningeal space. In human disease, cancer cells within the CSF produced C3 in correlation with clinical course. C3 expression in primary tumors was predictive of leptomeningeal relapse. Mechanistically, we found that cancer-cell-derived C3 activates the C3a receptor in the choroid plexus epithelium to disrupt the blood-CSF barrier. This effect allows plasma components, including amphiregulin, and other mitogens to enter the CSF and promote cancer cell growth. Pharmacologic interference with C3 signaling proved therapeutically beneficial in suppressing leptomeningeal metastasis in these preclinical models.
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What OpenQuestion holds
Registered trials
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.