胃癌微环境中TGF-β1对肿瘤相关巨噬细胞miR-155表达的影响

Effect of TGF-β1 from gastric cancer microenviroment on expression of miR-155 in tumor-associated macrophages

目的研究胃癌微环境中转化生长因子β1(TGF-β1)对肿瘤相关巨噬细胞中microRNA-155(miR-155)表达的影响。方法用免疫组织化学的方法检测人胃癌组织和癌旁正常胃组织中TGF-β1和M2型巨噬细胞表面分子CD163表达;用荧光定量PCR检测巨噬细胞内miR-155的表达。比较巨噬细胞、胃癌肿瘤相关巨噬细胞、用TGF-β1刺激的巨噬细胞及TGF-β1受体阻断剂刺激胃癌肿瘤相关巨噬细胞中的miR-155表达差异。结果胃癌肿瘤相关巨噬细胞内miR-155的表达低于正常巨噬细胞(P<0.05)。用TGF-β1受体阻断剂刺激后,胃癌肿瘤相关巨噬细胞内miR-155的表达升高(P<0.05);TGF-β1刺激的巨噬细胞中miR-155表达亦低于正常巨噬细胞(P<0.05)。CD163和TGF-β1的表达呈正相关(P<0.01)。结论胃癌细胞分泌的TGF-β1能下调巨噬细胞中的miR-155表达;提示其可通过下调巨噬细胞中miR-155的表达而促进巨噬细胞向M2型分化。

Objective To explore the effect of transforming growth factor（TGF）-β1from gastric cancer microenviroment on the expression of microRNA-155（miR-155）in tumor-associated macrophages.Methods The expressions of TGF-β1and M2 macrophage cell surface molecules CD163 were detected by immunohistochemistry in human gastric cancer tissues and tumor-adjacent normal gastric tissues.The expression of miR-155 in macrophages was detected using qRT-PCR.The difference of miR-155 expression among the macrophages,gastric cancer-related macrophages,the macrophages stimulated by TGF-β1,and the gastric cancer-related macrophages stimulated by TGF-β1receptor blocker was compared.Results The expression of miR-155 in gastric cancer-related macrophages was lower than that in normal macrophages（P〈0.05）,which was increased after stimulated by TGF-β1receptor blocker（P〈0.05）.The expression of miR-155 in the macrophages stimulated by TGF-β1was lower than that in normal macrophages（P〈0.05）.The expression of TGF-β1 was positively correlated to that of CD163（P〈0.01）.Conclusion TGF-β1secreted by gastric cancer cells can decrease miR-155 expression in macrophages,suggesting that TGF-β1in gastric cancer microenvironment may promote the differentiaion of macrophages to M2 macrophage by downregulating the expression of miR-155 in macrophages.