免疫学杂志2024,Vol.40Issue(8) :629-637.DOI:10.13431/j.cnki.immunol.j.20240088

脂多糖调控肿瘤相关成纤维细胞TLR4/NF-κB通路促进结肠癌细胞上皮间充质转化的研究

Regulation of TLR4/NF-κB pathway in tumor-associated fibroblasts by lipopolysaccharide promotes EMT in colon cancer cells

赵景文 张芯 李兆桓 王雅楠 徐明 高峰
免疫学杂志2024,Vol.40Issue(8) :629-637.DOI:10.13431/j.cnki.immunol.j.20240088

脂多糖调控肿瘤相关成纤维细胞TLR4/NF-κB通路促进结肠癌细胞上皮间充质转化的研究

Regulation of TLR4/NF-κB pathway in tumor-associated fibroblasts by lipopolysaccharide promotes EMT in colon cancer cells

赵景文 1张芯 2李兆桓 2王雅楠 3徐明 3高峰3
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作者信息

  • 1. 730050 兰州,中国人民解放军联勤保障部队第九四〇医院;730000 兰州,甘肃中医药大学
  • 2. 730000 兰州,甘肃中医药大学
  • 3. 730050 兰州,中国人民解放军联勤保障部队第九四〇医院
  • 折叠

摘要

目的 探讨肿瘤相关成纤维细胞(CAFs)通过TLR4/NF-κB通路对结肠癌细胞上皮间充质转化的影响.方法 建立结肠癌细胞和CAFs细胞共培养模型,以结肠癌细胞为对照组,共培养模型和脂多糖(LPS,15 μg/ml)干预共培养模型为实验组,Transwell实验观察结肠癌细胞的迁移情况;免疫荧光检测CAFs细胞中α-SMA、FAP和VEGF表达情况;Western blotting和RT-PCR分别检测CAFs细胞中TLR4、MyD88、NF-κB以及结肠癌细胞中E-cadherin、N-cadherin和Vimentin蛋白和mRNA表达情况.结果 CAFs细胞和结肠癌细胞共培养模型可以促进结肠癌细胞的迁移,提高了α-SMA、FAP在CAFs细胞中表达;结肠癌细胞的迁移与CAFs细胞中TLR4/NF-κB通路的激活有关,该通路激活后提高CAFs细胞中VEGF的表达,进一步促进结肠癌细胞EMT,增加癌细胞的迁移侵袭能力.结论 CAFs可促进结肠癌细胞的迁移,其机制可能与TLR4/NF-κB通路激活有关,CAFs表达VEGF细胞因子,从而促进结肠癌细胞上皮间充质转化.

Abstract

Objective To investigate the effect of TLR4/NF-κB pathway on epithelial mesenchymal transformation of colon cancer cells in tumor-associated fibroblasts.Methods A co-culture model of colon cancer cells and CAFs cells was established.Colon cancer cells were taken as control group,co-culture model and lipopoly Saccharide(LPS,15 μg/ml)co-culture model were taken as experimental group,and the migration of colon cancer cells was observed by transwell assay.the expressions of α-SMA,FAP and VEGF in CAFs cells were detected by immunofluorescence.the protein and mRNA expressions of TLR4、Myd88、NF-κB in CAFs cells and E-cadherin,N-cadherin、Vimentin in colon cancer cells were detected by Western blotting and RTPCR,respectively.Results The co-culture model of CAFs cells and colon cancer cells can promote the migration of colon cancer cells,and increase the expression of α-SMA and FAP in CAFs cells.the migration of colon cancer cells is related to the activation of TLR4/NF-κB pathway in CAFs cells,which enhances the expression of VEGF in CAFs cells,further promotes EMT of colon cancer cells,and increases the migration and invasion ability of cancer cells.Conclusion CAFs can promote the migration of colon cancer cells,and the mechanism may be related to the activation of TLR4/NF-κB pathway.CAFs express VEGF cytokines,thereby promoting epithelial mesenchymal transformation of colon cancer cells.

关键词

肿瘤相关成纤维细胞/结肠癌细胞/TLR4/NF-κB通路/上皮间充质转化

Key words

Tumor-associated fibroblasts/Colon cancer cell/TLR4/NF-κB pathway/Epithelial mesenchymal transformation

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出版年

2024
免疫学杂志
第三军医大学,中国免疫学会

免疫学杂志

CSTPCD
影响因子:0.704
ISSN:1000-8861
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