ArticleCell communication and signaling : CCS2021
Chronic inflammation of middle ear cholesteatoma promotes its recurrence via a paracrine mechanism.
Article in Cell communication and signaling : CCS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Article
- Benign, persistent, and invasive: mechanistic and translational approaches to middle‑ear cholesteatoma.Exploration of targeted anti-tumor therapy · 2026Review
- Cholesteatoma: An Updated Review of Molecular Pathogenesis and Potential Therapeutic Directions.Current medicinal chemistry · 2026Review
- Identification of Differential Metabolites in Chronic Suppurative Otitis Media With Non-Targeted and Targeted Metabolomics Approach.Smart medicine · 2025Article
- Genetic risk score for cholesteatoma recurrence: using UK Biobank data toward more individualized patient management.International journal of molecular epidemiology and genetics · 2025Article
- Expression of periostin in the epithelium of cholesteatoma with different degrees of ossicular chain destruction and its clinical value in predicting postoperative hearing recovery.Biomedical engineering online · 2024Article
- Evaluation of the Role of Myofibroblast and Fibronectin in the Aetiopathogenesis of Cholesteatoma.Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India · 2024Article
- Osteopontin-driven partial epithelial-mesenchymal transition governs the development of middle ear cholesteatoma.Cell cycle (Georgetown, Tex.) · 2024Article
- Cholesteatoma Severely Impacts the Integrity and Bone Material Quality of the Incus.Calcified tissue international · 2023Article
- The Hyperproliferation Mechanism of Cholesteatoma Based on Proteomics: SNCA Promotes Autophagy-Mediated Cell Proliferation Through the PI3K/AKT/CyclinD1 Signaling Pathway.Molecular & cellular proteomics : MCP · 2023Article
- Imaging guidance for cholesteatoma surgery using tissue autofluorescence.Journal of biomedical optics · 2023Article
- Review of potential medical treatments for middle ear cholesteatoma.Cell communication and signaling : CCS · 2022Review
- The Relationship between the M1/M2 Macrophage Polarization and the Degree of Ossicular Erosion in Human Acquired Cholesteatoma: An Immunohistochemical Study.Journal of clinical medicine · 2022Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCholesteatoma disease is an expanding lesion in the middle ear. Hearing loss and facial paralysis alongside with other intracranial complications are found. No pharmaceutical treatment is available today and recurrence after surgical extraction occurs. We investigated possible TLR4-based mechanisms promoting recurrence and explore possible treatments strategies.
methodsWe isolated fibroblasts and epidermal stem cells from cholesteatoma tissue and healthy auditory canal skin. Subsequently, their expression under standard culture conditions and after stimulation with LPS was investigated by RT-qPCR. Cell metabolism and proliferation were analysed upon LPS treatment, with and without TLR4 antagonist. An indirect co-culture of fibroblasts and epidermal stem cells isolated from cholesteatoma tissue was utilized to monitor epidermal differentiation upon LPS treatment by RT-qPCR and immunocytochemistry.
resultsUnder standard culture conditions, we detected a tissue-independent higher expression of IL-1β and IL-8 in stem cells, an upregulation of KGF and IGF-2 in both cell types derived from cholesteatoma and higher expression of TLR4 in stem cells derived from cholesteatoma tissue. Upon LPS challenge, we could detect a significantly higher expression of IL-1α, IL-1β, IL-6 and IL-8 in stem cells and of TNF-a, GM-CSF and CXCL-5 in stem cells and fibroblasts derived from cholesteatoma. The expression of the growth factors KGF, EGF, EREG, IGF-2 and HGF was significantly higher in fibroblasts, particularly when derived from cholesteatoma. Upon treatment with LPS the metabolism was elevated in stem cells and fibroblasts, proliferation was only enhanced in fibroblasts derived from cholesteatoma. This could be reversed by the treatment with a TLR4 antagonist. The cholesteatoma fibroblasts could be triggered by LPS to promote the epidermal differentiation of the stem cells, while no LPS treatment or LPS treatment without the presence of fibroblasts did not result in such a differentiation.
conclusionWe propose that cholesteatoma recurrence is based on TLR4 signalling imprinted in the cholesteatoma cells. It induces excessive inflammation of stem cells and fibroblasts, proliferation of perimatrix fibroblasts and the generation of epidermal cells from stem cells thru paracrine signalling by fibroblasts. Treatment of the operation site with a TLR4 antagonist might reduce the chance of cholesteatoma recurrence. Video Abstract.
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