What does this research mean for the field?

MMP1 regulates head and neck squamous cell carcinoma progression and therapeutic response by influencing microbiome-mediated immune remodeling, inflammation, and angiogenesis within the tumor microenvironment. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to clarify how MMP1 influences head and neck squamous cell carcinoma progression and treatment response.

May 17, 2026Open Access

MMP1 Modulates Head and Neck Squamous Cell Carcinoma Progression and Therapeutic Response Via Tumour Microenvironment

Key Points

This research aims to clarify how MMP1 influences head and neck squamous cell carcinoma progression and treatment response.
Conducted transcriptomic analysis of HNSCC tissues and functional experiments in Cal-27 cells using a zebrafish tumour model.
Evaluated effects of MMP1 knockdown, TPF chemotherapy, and Bifidobacterium longum on cancer cell behavior.
Assessed macrophage recruitment, proinflammatory cytokine expression, and gut microbiota diversity.
MMP1 was up-regulated in tumours, correlating with invasion and metastasis.
Knockdown of MMP1 decreased efficacy of TPF, B. longum and their combination, affecting tumour growth and immune function.
B. longum partially mitigated MMP1's role in immune activation, highlighting microbial-immune interactions.

Abstract

AIM: Head 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. METHODS: We 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. RESULTS: Transcriptomic 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. CONCLUSION: Our 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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