ArticleInternational dental journal2026
MMP1 Modulates Head and Neck Squamous Cell Carcinoma Progression and Therapeutic Response Via Tumour Microenvironment.
Article in International dental journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
aimHead and neck squamous cell carcinoma (HNSCC) is a highly invasive malignancy driven by complex molecular interactions within the tumour microenvironment (TME). This study aimed to investigate the critical role of MMP1 in HNSCC progression, particularly its interplay with the microbiome and immune remodelling, to uncover potential therapeutic targets.
methodsWe conducted transcriptomic analysis of HNSCC tissues and performed functional experiments in Cal-27 cells using a zebrafish tumour model, including MMP1 knockdown. The effects of TPF chemotherapy, Bifidobacterium longum, and their combination were evaluated in vitro. Additionally, we assessed macrophage recruitment, proinflammatory cytokine expression (IL-6, IL-1B, TNF-A), angiogenesis-related genes (VEGFA), zebrafish transcriptomic profiles, and gut microbiota diversity.
resultsTranscriptomic profiling revealed significant gene expression differences between cancer and healthy tissues, with enrichment in metabolic, neurodegenerative, and cardiovascular pathways. MMP1 was markedly up-regulated in tumours and strongly correlated with invasion and metastasis. Functional studies demonstrated that MMP1 knockdown reduced the efficacy of TPF, B. longum, and their combination, impairing tumour growth suppression, macrophage recruitment, and proinflammatory cytokine expression. However, B. longum partially counteracted MMP1-mediated immune activation, suggesting microbial-immune crosstalk. MMP1 knockdown also retained partial inhibition of angiogenesis-related genes (eg, VEGFA), indicating a selective role in vascular remodelling. Furthermore, MMP1 knockdown attenuated the Cal-27 cell-induced reduction in zebrafish gut microbiome diversity and alterations in transcriptomic expression patterns.
conclusionOur findings establish MMP1 as a key regulator of HNSCC progression and therapeutic response, influencing microbiome-mediated immune remodelling, inflammation, and angiogenesis. These insights suggest that targeting MMP1 and modulating the microbiome could enhance therapeutic strategies for HNSCC by reshaping the TME. This study provides a foundation for further exploration of TME-targeted interventions in HNSCC treatment.
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