2. Academic Validation
  3. Chronic inflammation promotes gastric cancer progression via ADAM10-mediated cleavage of CX3CL1

Chronic inflammation promotes gastric cancer progression via ADAM10-mediated cleavage of CX3CL1

  • Sci Rep. 2026 Feb 15;16(1):9169. doi: 10.1038/s41598-026-39743-6.
Zhiyuan Song # 1 2,  Yueying Liu # 1 2,  Zan Wang # 1 2,  Sicheng Zhao 1 2,  Jingcheng Zhang 1 2,  Yunhai Wei 3,  Zhengqi Zhao 1 2,  Tao Jiang 4 5,  Guangji Zhang 6 7
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
  • 2 Key Laboratory of Blood-stasis-toxin Syndrome of Zhejiang Province, Hangzhou, 310053, China.
  • 3 Huzhou Central Hospital, Affliated Central Hospital Huzhou University, Huzhou, 313000, China.
  • 4 School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China. [email protected].
  • 5 Key Laboratory of Blood-stasis-toxin Syndrome of Zhejiang Province, Hangzhou, 310053, China. [email protected].
  • 6 School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China. [email protected].
  • 7 Key Laboratory of Blood-stasis-toxin Syndrome of Zhejiang Province, Hangzhou, 310053, China. [email protected].
  • # Contributed equally.
PMID: 41691064 DOI: 10.1038/s41598-026-39743-6
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.

Keywords

ADAM10; CX3CL1; Chronic inflammation; Gastric cancer.

Figures
Products