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

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。

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.