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肿瘤相关巨噬细胞促进上皮性卵巢癌迁移和侵袭能力的机制研究

Mechanism of tumor-associated macrophages promoting the migration and invasion of epithelial ovarian cancer

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【作者】 孟凡荣王秀艳陈琛史云芳李晓洲琚端李岩潘红丽李雪冰张颖

【Author】 MENG Fan-rong;WANG Xiu-yan;CHEN Chen;SHI Yun-fang;LI Xiao-zhou;JU Duan;LI Yan;PAN Hong-li;LI Xue-bing;ZHANG Ying;General Hospital of Tianjin Medical University;

【通讯作者】 张颖;

【机构】 天津医科大学总医院

【摘要】 目的研究肿瘤相关巨噬细胞(TAMs)对上皮性卵巢癌迁移和侵袭能力的影响及其可能的调控机制。方法利用巨噬细胞集落刺激因子(M-CSF)和白细胞介素-4(IL-4)对小鼠骨髓巨噬细胞进行诱导,使其分化为M2型TAMs;将TAMs与卵巢癌细胞共培养,检测其上皮间质转化(EMT)相关分子的表达;观察卵巢癌细胞局部黏着斑激酶(FAK)和基质金属蛋白酶家族(MMPs)的表达变化情况。结果获得稳定表达的M2型TAMs;将TAMs与卵巢癌细胞共培养后,卵巢癌细胞的迁移和侵袭能力增强;EMT相关分子E-cadherin表达降低,间质标志蛋白N-cadherin和Vimentin的表达升高;TAMs刺激后卵巢癌细胞的FAK、MMP-2和MMP-9的蛋白表达量明显增加。结论 TAMs与上皮性卵巢癌的迁移和侵袭相关,TAMs可能通过调控EMT、FAK及MMPs等的表达促进上皮性卵巢癌的迁移和侵袭。

【Abstract】 Objective To determine the effect of tumor-associated macrophages (TAMs) on the migration and invasion of epithelial ovarian cancer and its possible regulatory mechanism.Methods Mouse bone marrow macrophages were induced by cytokine M-CSF and IL-4 to differentiate into M2 macrophage TAMs.TAMs were co-cultured with ovarian cancer cells to detect the expression of epithelial-mesenchymal transition (EMT) molecules.The changes of focal adhesion kinase (FAK) and matrix metalloproteinases (MMPs) in the ovarian cancer cells were observed.Results Stable expression of TAMs was obtained.TAMs were co-cultured with ovarian cancer cells,the migration and invasion of the ovarian cancer cells were enhanced,the expression of EMT-related molecules E-cadherin was decreased,and the expression of N-cadherin and Vimentin was increased.The expression levels of FAK,MMP-2,and MMP-9 in the ovarian cancer cells increased significantly.Conclusion M2 macrophages may promote the migration and invasion of epithelial ovarian cancer by regulating the expression of EMT,FAK and MMPs.

【基金】 国家自然科学基金项目(No.81302002);天津市自然科学基金项目(No.18JCYBJC92100,No.14JCQNJC12300,No.17JCQNJC11700);天津医科大学总医院孵育基金(No.ZYYFY2019022和No.ZYYFY2016013)
  • 【文献出处】 中南药学 ,Central South Pharmacy , 编辑部邮箱 ,2020年10期
  • 【分类号】R737.31
  • 【被引频次】2
  • 【下载频次】528
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