ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2023
Lineage Plasticity in SCLC Generates Non-Neuroendocrine Cells Primed for Vasculogenic Mimicry.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 21 citations in OpenAlex.
- NOTCH1 reverses immune suppression in small cell lung cancer through reactivation of STING.The Journal of clinical investigation · 2025Trial
- Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.Annals of medicine · 2026Review
- PAX5 modulates vascularization and contributes to neuroendocrine lineage transition during carcinoma progression.The Journal of clinical investigation · 2026Article
- Molecular phenotypes stratify small cell lung cancer for targeted therapy and immunotherapy.British journal of cancer · 2026Article
- RNA methyltransferase NSUN2 enhances vasculogenic mimicry and malignant progression of cervical cancer through upregulation of MMP-9.Oncology letters · 2026Article
- UHRF1 drives subtype-independent aggressiveness and immune evasion in small cell lung cancer through PRC2 interactions.iScience · 2026Article
- The FOXC2-LAMA4 Axis Orchestrates Vasculogenic Mimicry and Immunosuppressive Niche Formation to Drive Metastatic Cascade in Renal Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- Spliceosome inhibition induces Z-RNA and ZBP1-driven cell death in small cell lung cancer.Cell reports · 2025Article
- Extracellular matrix protein signaling promotes multi-step cancer vasculogenic mimicry formation.Cell communication and signaling : CCS · 2025Article
- Cancer-associated fibroblasts expressing FSTL3 promote vasculogenic mimicry formation and drive colon cancer malignancy.Cell death & disease · 2025Article
- Circulating Tumor Cells Shed Shearosome Extracellular Vesicles in Capillary Bifurcations That Activate Endothelial and Immune Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- DDX5 super-enhancer promotes vasculogenic mimicry formation and metastasis in nasopharyngeal carcinoma by enhancing ADAM10 transcription.Cell reports. Medicine · 2025Article
- Challenges of small cell lung cancer heterogeneity and phenotypic plasticity.Nature reviews. Cancer · 2025Review
- Circulating tumor cells shed shearosome extracellular vesicles in capillary bifurcations that activate endothelial and immune cells.bioRxiv : the preprint server for biology · 2025Article
- Tumor Heterogeneity and Plasticity in Small Cell Lung Cancer.Lung Cancer (Auckland, N.Z.) · 2025Review
- Small cell lung cancer with liver metastases: from underlying mechanisms to treatment strategies.Cancer metastasis reviews · 2024Review
- Review
- Small cell lung cancer profiling: an updated synthesis of subtypes, vulnerabilities, and plasticity.Trends in cancer · 2024Review
- Molecular subtypes and prognostic factors of lung large cell neuroendocrine carcinoma.Translational lung cancer research · 2024Article
Corrections and comments
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Authors and funding
27 authors at 7 institutions in 2 countries.
Funding
Abstract
introductionVasculogenic mimicry (VM), the process of tumor cell transdifferentiation to endow endothelial-like characteristics supporting de novo vessel formation, is associated with poor prognosis in several tumor types, including SCLC. In genetically engineered mouse models (GEMMs) of SCLC, NOTCH, and MYC co-operate to drive a neuroendocrine (NE) to non-NE phenotypic switch, and co-operation between NE and non-NE cells is required for metastasis. Here, we define the phenotype of VM-competent cells and molecular mechanisms underpinning SCLC VM using circulating tumor cell-derived explant (CDX) models and GEMMs.
methodsWe analyzed perfusion within VM vessels and their association with NE and non-NE phenotypes using multiplex immunohistochemistry in CDX, GEMMs, and patient biopsies. We evaluated their three-dimensional structure and defined collagen-integrin interactions.
resultsWe found that VM vessels are present in 23/25 CDX models, 2 GEMMs, and in 20 patient biopsies of SCLC. Perfused VM vessels support tumor growth and only NOTCH-active non-NE cells are VM-competent in vivo and ex vivo, expressing pseudohypoxia, blood vessel development, and extracellular matrix organization signatures. On Matrigel, VM-primed non-NE cells remodel extracellular matrix into hollow tubules in an integrin β1-dependent process.
conclusionsWe identified VM as an exemplar of functional heterogeneity and plasticity in SCLC and these findings take considerable steps toward understanding the molecular events that enable VM. These results support therapeutic co-targeting of both NE and non-NE cells to curtail SCLC progression and to improve the outcomes of patients with SCLC in the future.
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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.