TY  - EJOU
AU  - Bai, Shaoxiong 
AU  - Duan, Yilei 
AU  - Yao, Tian 
AU  - Shi, Yanan 
AU  - Zhang, Xin 
AU  - Ma, Xiaole 
AU  - Jia, Kai 

TI  - Gastric Cancer-Derived Exosomes Activate Mast Cells via the SCF/c-KIT Pathway to Drive Angiogenesis and Metastasis
T2  - Oncology Research

PY  - 2026
VL  - 34
IS  - 10
SN  - 1555-3906

AB  - <b>Background:</b> Exosomes mediate intercellular communication within the tumor microenvironment. However, their role in modulating mast cell activity in gastric cancer (GC) remains unclear. This study aimed to elucidate whether GC-derived exosomes activate mast cells via the SCF/c-KIT pathway to promote angiogenesis and metastasis, and to assess the therapeutic potential of targeting this axis. <b>Methods:</b> Exosomes were isolated from GC cell lines (AGS, MKN1), a normal gastric epithelial cell line (GES-1), and mouse gastric tumor tissues, followed by characterization via NTA, TEM, and western blot. Mast cell (LAD2) degranulation was quantified by β-hexosaminidase release and ELISA. Cell recruitment was evaluated using Transwell migration assays, and angiogenesis was assessed by tube formation assay. Underlying signaling pathways were analyzed by Western blot. The functional role of the SCF/c-KIT axis was investigated using shRNA-mediated knockdown and neutralizing antibodies. A mouse model of gastric cancer lung metastasis was established to validate the <i>in vivo</i> effects. <b>Results:</b> GC-derived exosomes, but not GES-1-derived ones, were enriched with SCF and induced mast cell recruitment, degranulation, and tryptase release via SCF/c-KIT activation. Mast cell-derived tryptase promoted angiogenesis by activating the MAPK pathway and upregulating VEGF in endothelial cells. <i>In vivo</i>, tumor-derived exosomes accelerated lung metastasis and angiogenesis, effects abrogated by a c-KIT blocking antibody, confirming SCF/c-KIT dependence. <b>Conclusion:</b> Gastric cancer-derived exosomes deliver SCF to activate mast cells via the c-KIT receptor, thereby fostering angiogenesis and metastasis. Targeting the exosomal SCF/c-KIT signaling axis may offer a promising therapeutic strategy to impede gastric cancer progression.
KW  - Gastric cancer; exosome; mast cell; angiogenesis; cancer metastasis

DO  - 10.32604/or.2026.085030