ArticleBritish journal of cancer2014
Senescent cancer-associated fibroblasts secrete active MMP-2 that promotes keratinocyte dis-cohesion and invasion.
Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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81 citing papers in PubMed, 138 citations in OpenAlex.
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- A Novel CAF-Related Signature for Precise Prediction of Clinical Outcomes and Immunotherapy Response for Breast Cancer Patients: Based on Multiomics Analyses and Experimental Validation.Mediators of inflammation · 2026Article
- Fibroblast transformation in the tumor microenvironment of lung adenocarcinoma: heterogeneity, regulation, and therapeutic targeting.Frontiers in immunology · 2026Review
- Cellular Senescence as a Risk Factor in Head and Neck Cancer-Diagnostic and Therapeutic Perspective.Cancers · 2025Review
- The emerging role of cancer-associated fibroblasts in hematological malignancies: from their influence on tumor progression and drug resistance to novel therapeutic opportunities.Clinical and experimental medicine · 2025Review
- The controversial role of senescence-associated secretory phenotype (SASP) in cancer therapy.Molecular cancer · 2025Review
- Optimizing Anti-PD1 Immunotherapy: An Overview of Pharmacokinetics, Biomarkers, and Therapeutic Drug Monitoring.Cancers · 2025Review
- Immune Evasion in Head and Neck Squamous Cell Carcinoma: Roles of Cancer-Associated Fibroblasts, Immune Checkpoints, andCancers · 2025Review
- Cancer-associated fibroblasts in cancer drug resistance and cancer progression: a review.Cell death discovery · 2025Review
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- The Role of Senescence, its Therapeutic Relevance and Clinical Implications in the Tumor Microenvironment.Theranostics · 2025Review
- Cancer-associated fibroblasts: dual roles from senescence sentinels to death regulators and new dimensions in therapy.Frontiers in immunology · 2025Review
- Bilayer 3D co-culture platform inducing the differentiation of normal fibroblasts into cancer-associated fibroblast like cells: New in vitro source to obtain cancer-associated fibroblasts.Bioengineering & translational medicine · 2025Article
- Matrix-free human lung organoids derived from induced pluripotent stem cells to model lung injury.Stem cell research & therapy · 2024Article
- Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment.Cancer communications (London, England) · 2024Review
- Hydrogen Therapy Reverses Cancer-Associated Fibroblasts Phenotypes and Remodels Stromal Microenvironment to Stimulate Systematic Anti-Tumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The Role of Aging and Senescence in Immune Checkpoint Inhibitor Response and Toxicity.International journal of molecular sciences · 2024Review
- Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrevious studies have demonstrated that senescent cancer-associated fibroblasts (CAFs) derived from genetically unstable oral squamous cell carcinomas (GU-OSCC), unlike non-senescent CAFs from genetically stable carcinomas (GS-OSCC), promoted keratinocyte invasion in vitro in a paracrine manner. The mechanism by which this occurs is unclear.
methodsPrevious work to characterise the senescent-associated secretory phenotype (SASP) has used antibody arrays, technology that is limited by the availability of suitable antibodies. To extend this work in an unbiased manner, we used 2D gel electrophoresis and mass spectroscopy for protein identification. Matrix metalloproteinases (MMPs) were investigated by gelatin zymography and western blotting. Neutralising antibodies were used to block key molecules in the functional assays of keratinocyte adhesion and invasion.
resultsAmong a variety of proteins that were differentially expressed between CAFs from GU-OSCC and GS-OSCC, MMP-2 was a major constituent of senescent CAF-CM derived from GU-OSCC. The presence of active MMP-2 was confirmed by gelatine zymography. MMP-2 derived from senescent CAF-CM induced keratinocyte dis-cohesion and epithelial invasion into collagen gels in a TGF-β-dependent manner.
conclusionsSenescent CAFs from GU-OSCC promote a more aggressive oral cancer phenotype by production of active MMP-2, disruption of epithelial adhesion and induction of keratinocyte invasion.
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