肿瘤相关血管内皮细胞对单核细胞趋化的影响

Effect of Tumor Associated Vascular Endothelial Cells on Monocyte Chemotaxis

目的:探究头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中肿瘤相关巨噬细胞(tumorassociated macrophage,TAM)的来源和极化机制。方法:用HNSCC的条件培养基将血管内皮细胞(vascular endothelial cells,VEC)诱导为肿瘤相关VEC,使用显微镜观察肿瘤相关VEC的形态,以RT-qPCR检测单核细胞趋化因子在肿瘤相关内皮细胞的表达,Transwell趋化实验检测肿瘤相关内皮细胞对单核细胞的趋化能力。进一步使用佛波酯(phorbol 12-myristate 13-acetate,PMA)将人单核细胞(THP-1)诱导为贴壁的巨噬细胞,与肿瘤相关内皮细胞共培养后,qRT-PCR检测巨噬细胞极化相关基因的表达。结果:HNSCC相关VEC形态呈多角形,细胞间连接疏松,排列紊乱,并分泌多种单核细胞趋化因子将单核细胞趋化至肿瘤微环境,同时将其极化为白细胞介素-10(IL-10)、精氨酸酶1(arginase 1,Arg-1)高表达的M2型TAM。结论:在HNSCC中,肿瘤相关VEC招募单核细胞并将其极化为M2型TAM。

Objective:To investigate the origin and polarization mechanism of TAM(tumor-associated macrophage)in squamous cell carcinoma of head and neck.Methods:The vascular endothelial cells were induced into tumor related vascular endothelial cells through the conditioned medium of head and neck squamous cell carcinoma cells.The morphology of tumor related vascular endothelial cells was observed by microscope,the expression of monocyte chemokine in tumor related endothelial cells was detected by qRT-PCR,and the chemotaxis ability of tumor related endothelial cells to monocytes was detected by transwell chemotaxis test.Furthermore,(phorbol 12-myristate 13-acetate,PMA)was used to induce THP-1 monocytes into adherent macrophages.After co-culture with tumor related endothelial cells,qRT-PCR was used to detect the expression of macrophage polarization related genes.Results:The endothelial cells associated with head and neck squamous cell carcinoma were polyhedral in shape,with loose intercellular connections and disordered arrangement,and secreted a variety of monocyte chemokines to recruit the monocytes to the tumor microenvironment,at the same time,they were polarized into M2 TAM with high expression of IL-10 and Arg-1.Conclusion:In squamous cell carcinoma of head and neck,tumor associated vascular endothelial cells recruit monocytes and polarize them to M2 TAM.