ArticleNature cell biology2025
Metastatic medulloblastoma remodels the local leptomeningeal microenvironment to promote further metastatic colonization and growth.
Article in Nature cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Niches in cancer: from primary tumors to metastatic disease.Journal of hematology & oncology · 2026Review
- The Origin of Cancer-Associated Fibroblasts (CAFs) in Brain Metastases: Seven Hypotheses and Current Evidence.Cancers · 2026Review
- From developmental origins to relapse: molecular and therapeutic insights in medulloblastoma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Review
- Meningeal-tumor interactions define distinct modes of leptomeningeal colonization in Group 3 medulloblastoma.Acta neuropathologica communications · 2026Article
- Noncoding RNAs in Pediatric Solid Tumors: Advances in Understanding and Critical Knowledge Gaps.Cells · 2026Review
- Medulloblastoma stem cell programs: Molecular roadmaps of disease progression.Developmental cell · 2026Review
- The tumor microenvironment of medulloblastoma: from emerging biological insights to novel therapeutic targeting.Frontiers in oncology · 2026Review
- The Leptomeningeal Microenvironment in Metastasis: A Unique Central Nervous System Niche.Annals of Indian Academy of Neurology · 2026Article
- Clonal evolution and stromal crosstalk drive an invasive epithelial program in bladder cancer.Frontiers in cell and developmental biology · 2026Article
- National multicentered retrospective review of salvage therapy for pediatric medulloblastoma: a Canadian experience.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2025Article
- Allograft transplantation for Drosophila tumor metastasis studies.Disease models & mechanisms · 2025Article
- Metastatic medulloblastoma remodels the local leptomeningeal microenvironment to promote further metastatic colonization and growth.Nature cell biology · 2025Article
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Authors and funding
41 authors.
Funding
Abstract
Leptomeningeal metastases are the major source of morbidity and mortality for patients with medulloblastoma. The biology of the leptomeningeal metastases and the local tumour microenvironment are poorly characterized. Here we show that metastasis-associated meningeal fibroblasts (MB-MAFs) are transcriptionally distinct and signal extensively to tumour cells and the tumour microenvironment. Metastatic cells secrete platelet-derived growth factor (PDGF) ligands into the local microenvironment to chemotactically recruit meningeal fibroblasts. Meningeal fibroblasts are reprogrammed to become MB-MAFs, expressing distinct transcriptomes and secretomes, including bone morphogenetic proteins. Active bone morphogenetic protein signalling and co-implantation of tumour cells with MB-MAFs enhances the colonization of the leptomeninges by medulloblastoma cells and promotes the growth of established metastases. Furthermore, treatment of patient-derived xenograft mice with a PDGF-receptor-α neutralizing antibody enhances overall survival in vivo. Collectively, our results define a targetable intercellular communication cascade in the metastatic niche to treat leptomeningeal disease.
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