贝伐单抗激活M2巨噬细胞促进肿瘤转移

Bevacizumab promotes cancer metastasis by activating M2 macrophage

目的研究贝伐单抗与肿瘤微环境中的巨噬细胞间相互关系,初步探讨临床贝伐单抗治疗肝癌无效的机制。方法采用免疫组化检测肝癌微环境中巨噬细胞表型。巨噬细胞与肿瘤细胞共培养体系中加入贝伐单抗,采用酶联免疫吸附测定(ELISA)方法检测培养体系中炎症因子及血管生长因子的分泌。采用划痕实验检测共培养体系上清对肿瘤细胞迁移的影响。结果临床标本检测肿瘤微环境中的巨噬细胞为M2型,贝伐单抗显著增加M2型巨噬细胞与肿瘤细胞共培养体系中炎症因子转化生长因子-β(TGF-β)、白细胞介素-10(IL-10)、白细胞介素-12(IL-10)及血管内皮生长因子(VEGF)的水平,肿瘤细胞迁移显著增加。结论贝伐单抗激活M2型巨噬细胞,促进炎症因子及血管生长因子分泌,促进肿瘤细胞迁移。

Objective To study the relationship between bevacizumab,macrophages,and tumor cells in the tumor microenvironment, and find the potential mechanism of invalid treatment of bevacizumab in HCC （ hepatic cell carcinoma）. Methods The phenotype of macrophages in HCC was determined by immunohistochemistry. M2 macrophages and tumor cells were cocuhured and bevacizumab was added.The release of inflammatory cytokines and vascular growth factor were detected by ELISA.The impact of supernant from cocuhure system on tumor cell migration was detected.Results Most macrophages in HCC microenvironment had M2 characteristics. Bevacizunmb increased the level of inflammatory cytokines and vascular endothelial growth factor （ VEGF） significantly in the M2 macrophages and tumor cells cocuhure system.Supernant from M2 macrophages and tumor cells coculture system promoted tumor cell migration.Conclusion Bevacizumab can activate M2 macrophage and promote cancer metastasis.