临床与病理杂志2025，Vol.45Issue(2)：127-137,11.DOI:10.11817/j.issn.2095-6959.2025.240269
施万细胞对胃癌细胞增殖和迁移的影响
Effects of Schwann cells on the proliferation and migration of gastric cancer cells
摘要
Abstract
Objective:Schwann cells(SCs),the predominant glial cells in the peripheral nervous system,play a significant role in promoting the development and progression of malignant tumors.This study aims to investigate the effects of SCs on the proliferation and migration of gastric cancer cell lines HGC-27,BGC-823,and AGS. Methods:Hematoxylin-eosin(HE)staining and immunohistochemistry(IHC)were used to observe the relationship between peripheral nerve fibers and gastric cancer cells in tumor tissues.Primary rat SCs were cultured in serum-free high-glucose DMEM to produce conditioned medium(CM).The experiment was divided into a co-culture group(CM group)and a negative control group(NC group).The CM group used SCs CM to culture gastric cancer cells;in the NC group,the gastric cancer cells were cultured using DMEM medium.The effects of SCs CM on the proliferation and migration abilities of gastric cancer cells were respectively detected by the cell proliferation assay and the cell scratch assay of cell counting kit-8(CCK-8).The co-culture system of gastric cancer cells and SCs was constructed using Transwell chambers,the experiment was divided into a co-culture group and a NC group.In the co-culture group,the gastric cancer cells and SCs were cultured respectively in the upper and lower layers of the Transwell chamber;in the NC group,the gastric cancer cells were cultured in the upper layer of the Transwell chamber,and the lower layer was DMEM medium.The effect of SCs on the migration ability of gastric cancer cells was detected by counting the number of gastric cancer cells passing through the small hole.Bioinformatics analysis was performed to identify the key regulatory molecules and specific receptors associated with SC dedifferentiation,and their expression and localization in SCs and gastric cancer cells were examined. Results:HE and IHC results revealed that gastric cancer cells surrounded and even invaded the peripheral nerve fibers,indicating perineural invasion.The CCK-8 cell proliferation assay and cell scratch assay showed that:compared with the NC group,the proliferation and migration abilities of gastric cancer cells in the CM group were significantly enhanced(both P<0.05).The Transwell co-culture experiment showed that:compared with the NC group,the migration ability of gastric cancer cells in the co-culture group was significantly improved(P<0.05).Bioinformatics analysis indicated that glial cell-derived neurotrophic factor(GDNF)was significantly upregulated in dedifferentiated SCs.Western blotting confirmed increased GDNF expression in SCs cultured in serum-free high-glucose DMEM.Immunofluorescence staining showed that GDNF was predominantly expressed in peripheral nerve fibers within gastric cancer tissues.GDNF family receptor alpha 1(GFRα-1)was also found to be highly expressed in gastric cancer tissues. Conclusion:SCs significantly promote the proliferation and migration of gastric cancer cells,and the GDNF-GFRα-1 axis may play a crucial regulatory role in this process.关键词
施万细胞/胃癌/增殖/迁移/肿瘤微环境Key words
Schwann cells/gastric cancer/proliferation/migration/tumor microenvironment引用本文复制引用
兰东旭,谢鸣杰,仲铭洋,于卓群,吴寒,顾琪琪..施万细胞对胃癌细胞增殖和迁移的影响[J].临床与病理杂志,2025,45(2):127-137,11.基金项目
中国遗传资源保护与疾病防控教育部重点实验室开放课题(LPHGRD2024-003).This work was supported by the Open Project Program of Key Laboratory of Preservation of Human Genetic Resources and Disease Control of China,Ministry of Education(LPHGRD2024-003). （LPHGRD2024-003）
