Academic Journal
Saliva from oral squamous cell carcinoma patients promotes tumor progression via Inflammation, stromal remodeling, and metabolic reprogramming in a mouse model.
| Τίτλος: | Saliva from oral squamous cell carcinoma patients promotes tumor progression via Inflammation, stromal remodeling, and metabolic reprogramming in a mouse model. |
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| Συγγραφείς: | Zhang XY; School and Hospital of Stomatology, Hebei Medical University, Shijiazhuang, China.; Hebei Technology Innovation Center of Oral Health, Shijiazhuang, China., Li YT; School and Hospital of Stomatology, Hebei Medical University, Shijiazhuang, China., Guo J; The Fourth Hospital of Hebei Medical University, Shijiazhuang, China., Feng Y; School and Hospital of Stomatology, Hebei Medical University, Shijiazhuang, China.; Hebei Technology Innovation Center of Oral Health, Shijiazhuang, China., Han Q; Hebei Medical University, Shijiazhuang, China., Zhang SH; School and Hospital of Stomatology, Hebei Medical University, Shijiazhuang, China., Gao Y; Hebei Provincial Traditional Chinese Medicine Hospital, Shijiazhuang, China., Yin HT; School and Hospital of Stomatology, Hebei Medical University, Shijiazhuang, China., Ding XX; Xinle Hospital of Traditional Chinese Medicine, Shijiazhuang, China., Li XJ; School and Hospital of Stomatology, Hebei Medical University, Shijiazhuang, China. lixiangjun@hebmu.edu.cn.; Hebei Technology Innovation Center of Oral Health, Shijiazhuang, China. lixiangjun@hebmu.edu.cn., Liang BB; School and Hospital of Stomatology, Hebei Medical University, Shijiazhuang, China. liangbeibei@hebmu.edu.cn. |
| Πηγή: | BMC oral health [BMC Oral Health] 2025 Dec 01; Vol. 26 (1), pp. 16. Date of Electronic Publication: 2025 Dec 01. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: BioMed Central Country of Publication: England NLM ID: 101088684 Publication Model: Electronic Cited Medium: Internet ISSN: 1472-6831 (Electronic) Linking ISSN: 14726831 NLM ISO Abbreviation: BMC Oral Health Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : BioMed Central, [2001- |
| Ιατρικοί όροι (MeSH): | Saliva*/microbiology , Saliva*/metabolism , Mouth Neoplasms*/pathology , Mouth Neoplasms*/metabolism , Mouth Neoplasms*/microbiology , Carcinoma, Squamous Cell*/metabolism , Carcinoma, Squamous Cell*/pathology , Inflammation*, Animals ; Mice ; Disease Progression ; Tumor Microenvironment ; Disease Models, Animal ; Humans ; Male ; Microbiota ; Metabolomics ; Metabolic Reprogramming |
| Περίληψη: | Background: Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy with increasing evidence implicating the oral microbiome and tumor microenvironment in its progression. However, the mechanistic impact of OSCC patient-derived saliva on tumor development remains poorly understood. Methods: We established an orthotopic OSCC mouse model and topically applied saliva collected from OSCC patients to assess its effects on tumor progression. Multi-omics analyses, including 16 S rRNA sequencing, tumor transcriptomics (RNA-seq), and metabolomics (LC-MS), were performed to explore changes in the oral microbiota, gene expression profiles, and metabolic pathways. Results: Treatment with OSCC patient saliva significantly accelerated tumor growth compared to controls. Saliva application altered the oral microbiota, most notably causing a significant enrichment of the genus Staphylococcus. Tumor transcriptomics revealed upregulation of genes associated with chronic neutrophilic inflammation (Mpo), cancer-associated fibroblast (CAF) activation, and extracellular matrix (ECM) remodeling (Angptl4, Col2a1). Metabolomic analysis demonstrated profound metabolic reprogramming within the tumors, including enhanced amino acid metabolism (tryptophan, glutamate), fatty acid oxidation, and accumulation of the oncometabolite succinate. Integrated analysis showed that Staphylococcus abundance was strongly correlated with these inflammatory and metabolic signatures. Conclusions: This study demonstrates that saliva from OSCC patients promotes tumor progression in vivo through a multifactorial mechanism involving inflammation, stromal remodeling, and metabolic rewiring. These findings highlight the tumor-promoting potential of salivary and microbial components, suggesting new avenues for diagnostic and therapeutic strategies targeting the oral microenvironment in OSCC. (© 2025. The Author(s).) |
| Competing Interests: | Declarations. Ethics approval and consent to participate: Our study adhered to the Declaration of Helsinki, specifies the approving ethics committee with its reference number, and describes the process of obtaining informed consent. The collection and use of these human tissue samples were strictly conducted in accordance with the guidelines approved by the Ethics Committee of the School and Hospital of Stomatology, Hebei Medical University (IRB-ID: [2024]066), and informed consent was obtained from all patients prior to the study. All animal experiments were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee (IACUC) of Hebei Medical University (Ethics Approval Reference Number: [IACUC-Hebmu-P-2025393]). As the animals were commercially sourced specifically for biomedical research, informed consent from the owner was not applicable. All methods are reported in accordance with ARRIVE guidelines. Consent for publication: This manuscript does not contain any individual person’s data in any form (including any individual details, images, or videos). Competing interests: The authors declare no competing interests. |
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| Grant Information: | ZF2025241 Hebei Provincial Government-Funded Clinical Medicine Talent Cultivation Program; ZF2024151 Hebei Provincial Government-Funded Clinical Medicine Talent Cultivation Program; 2025350 Research projects under the Hebei Provincial Administration of Traditional Chinese Medicine; 20240101 Hebei Province Medical Science Research Project; 25297704D S&T Program of Hebei |
| Contributed Indexing: | Keywords: 16S rRNA; Metabolomics; Oral squamous cell carcinoma; RNA-seq; Tumor microenvironment |
| Entry Date(s): | Date Created: 20251201 Date Completed: 20260106 Latest Revision: 20260609 |
| Update Code: | 20260610 |
| PubMed Central ID: | PMC12771916 |
| DOI: | 10.1186/s12903-025-07413-0 |
| PMID: | 41327157 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1472-6831 |
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| DOI: | 10.1186/s12903-025-07413-0 |