Abstract
This study aimed to investigate the impact of chronic inflammation (CI) on gastric cancer (GC) progression and the underlying molecular mechanisms. A subcutaneous xenograft model using 615-strain mice was established to evaluate the pro-tumorigenic effects of CI. Proteome Profiler Mouse XL Cytokine Array was used to screen for key pro-tumorigenic cytokines induced by CI, and ELISA was employed for validation. single-cell RNA sequencing(ScRNA-seq) was performed to identify the cellular source of CX3CL1 in GC tumor tissues. CCK-8 and colony formation assays were used to assess the effect of CX3CL1 on GC cell proliferation, while wound-healing and Transwell assays evaluated cell migration. ADAM10 expression was measured in gastric cancer cells and tissues via qRT-PCR, Western blot, and immunofluorescence staining. CI significantly accelerated gastric cancer progression. CX3CL1 expression was markedly higher in GC tissues than in normal gastric tissues, and high CX3CL1 expression was associated with poor prognosis in GC patients. CX3CL1 recombinant protein significantly promoted the proliferation and migration of GC cells, and these effects were attenuated by pharmacological inhibition of CX3CR1. Mechanistically, CI upregulated the expression of ADAM10, which plays a key role in converting membrane-bound CX3CL1 to its soluble form. This study provided evidence that chronic inflammation could promote tumor progression through the activation of ADAM10/CX3CL1 axis in gastric cancer.
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Data availability
The single-cell RNA-seq raw sequencing data have been deposited in the NCBI Sequence Read Archive (SRA, an INSDC member repository) with accessions SRR37061229 and SRR37061230. BioProject: PRJNA1416616; BioSamples: SAMN54972753 and SAMN54972754. The processed single-cell expression matrices have been deposited in the Gene Expression Omnibus (GEO) under accession number GSE318425.
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Acknowledgements
The authors gratefully acknowledge the colleagues from the Laboratory of “Blood Stasis andToxin” Syndrome for their technical support and constructive discussions.
Funding
This study was supported by the Key Support Project of Regional Innovation and Development Joint Fund of National Natural Science Foundation of China (U23A20499); Zhejiang Provincial Natural Science Foundation of China (No. LQ23H270013); National Natural Science Foundation of China (No. 82204950); Key project of the National Nature Foundation of China (No. 82030119); Zhejiang Chinese Medicine University Chunyan Special Fund for the development of traditional Chinese medicine (No. CY202302); State Administration of Traditional Chinese Medicine Science and Technology Department - Zhejiang Provincial Administration of Traditional Chinese Medicine joint science and technology plan key research project (GZY-ZJ-KJ-23094).
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TJ, ZZ designed the experiment. ZS, YL and ZW conducted the experiment. ZS, ZW, SZ and JZ did the data analysis. ZS wrote the manuscript. YW, TJ and ZZ provided guidance during the experimentation phase and contributed to revising the manuscript. YW, TJ, GZ acquired funding. The authors read and approved the final manuscript.
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All animal care and experimental procedures adhered to the guidelines approved by the Animal Ethics Committee of Zhejiang Chinese Medical University (License Number: 20240115-04). All methods were carried out in accordance with relevant guidelines and regulations. All methods are reported in accordance with ARRIVE guidelines.
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Song, Z., Liu, Y., Wang, Z. et al. Chronic inflammation promotes gastric cancer progression via ADAM10-mediated cleavage of CX3CL1. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39743-6
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DOI: https://doi.org/10.1038/s41598-026-39743-6
