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肿瘤相关巨噬细胞对大网膜乳斑中胃癌干细胞及淋巴结微转移的影响

Effect of tumor-associated macrophages on gastric cancer stem cell in omental milky spots and lymph node micrometastasis.

作者信息

Zhang Chi, Hu Xiang, Liu Xiao-Yu, Liang Pin, Zhang Jian, Cao Liang, Wang Zheng-Lin, Liu Huan-Ran, Yin Xun-Guo, Dong Cheng-Yong, Wang Li-Ming

机构信息

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Dalian Medical Universiey Dalian, China.

Liaoning Laboratory of Cancer Genetics and Epigenetics, Department of Cell Biology, Dalian Medical University Dalian, China.

出版信息

Int J Clin Exp Pathol. 2015 Nov 1;8(11):13795-805. eCollection 2015.

Abstract

We observed whether the effect of tumor-associated macrophages on gastric cancer stem cell in omental milky spots and lymph nodes micrometastasis and research its possible mechanism. Macrophage THP-1 cells and Human gastric adenocarcinoma SGC-7901 cells were collectively cultivated in vivo. We found macrophage could suppress the proliferation and accelerated cell death of MFC cell. Meanwhile, these effects may be concerned with many signaling pathways, and we detected MCP-1 and COX-2 miRNA expressions, PGE-2 release levels, IL-4 and IL-10 activities, and TGF-β, IFN-γ, VEGF, MMP-2 and MMP-9 protein expressions in collectively cultivated cell. We found that MCP-1 and COX-2 miRNA expressions, and PGE-2 release levels were suppressed, IL-4 activity was inhibited and IL-10 activity was activated in collectively cultivated cell. Meanwhile, TGF-β, MMP-2 and MMP-9 protein expressions were inhibited and IFN-γ and VEGF protein expressions were activated in collectively cultivated cell. Taken together, these results suggest that the effect of tumor-associated macrophages on gastric cancer stem cell in omental milky spots and lymph nodes micrometastasis via COX-2/PGE-2/TGF-β/VEGF signal pathways.

摘要

我们观察肿瘤相关巨噬细胞对大网膜乳斑及淋巴结微转移中胃癌干细胞的影响,并研究其可能机制。将巨噬细胞THP-1细胞与人胃腺癌SGC-7901细胞进行体内共培养。我们发现巨噬细胞可抑制MFC细胞的增殖并加速其细胞死亡。同时,这些作用可能与多种信号通路有关,我们检测了共培养细胞中MCP-1和COX-2 miRNA表达、PGE-2释放水平、IL-4和IL-10活性以及TGF-β、IFN-γ、VEGF、MMP-2和MMP-9蛋白表达。我们发现共培养细胞中MCP-1和COX-2 miRNA表达及PGE-2释放水平受到抑制,IL-4活性被抑制而IL-10活性被激活。同时,共培养细胞中TGF-β、MMP-2和MMP-9蛋白表达受到抑制,IFN-γ和VEGF蛋白表达被激活。综上所述,这些结果表明肿瘤相关巨噬细胞通过COX-2/PGE-2/TGF-β/VEGF信号通路对大网膜乳斑及淋巴结微转移中的胃癌干细胞产生影响。

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