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目的研究肿瘤相关巨噬细胞(TAM)对鼻咽癌细胞转移的影响及其作用机制。方法采用免疫组织化学方法检测从中山大学肿瘤防治中心组织标本库选取的107例鼻咽癌组织TAM的表达情况。对单核-巨噬细胞进行培养并诱导分化,检测TAM的表面标记CD206的表达以及分泌CCL18的能力。应用Transwell实验检测与巨噬细胞共培养后的鼻咽癌细胞的侵袭、迁移能力。结果免疫组化结果显示,鼻咽癌中CD163~+/CD206~+肿瘤相关巨噬细胞广泛浸润,并且TAM的数目与鼻咽癌患者的不良预后相关。外周血中单核-巨噬细胞经过IL-4诱导分化后高表达特异性标志物CD206,并大量分泌CCL18,鉴定为M2型巨噬细胞。Transwell实验显示,与M2型巨噬细胞共培养的鼻咽癌细胞迁移、侵袭至下室的细胞明显多于对照组,差异有统计学意义(P<0.05)。结论肿瘤相关巨噬细胞的浸润与鼻咽癌不良预后相关,肿瘤相关巨噬细胞使鼻咽癌细胞的侵袭、迁移能力增加,可能是鼻咽癌转移的机制之一。
Objective To study the effect of tumor-associated macrophages (TAM) on the metastasis of nasopharyngeal carcinoma cells and its mechanism. Methods Immunohistochemistry was used to detect the expression of TAM in 107 cases of nasopharyngeal carcinoma selected from the tissue specimen library of Sun Yat-sen University Cancer Center. Mononuclear-macrophages were cultured and induced to differentiate, the expression of surface marker CD206 of TAM and the ability to secrete CCL18 were examined. Transwell assay was used to detect the invasion and migration of nasopharyngeal carcinoma cells co-cultured with macrophages. Results Immunohistochemistry showed that CD163 ~ + / CD206 ~ + tumor-associated macrophages were extensively infiltrated in nasopharyngeal carcinoma, and the number of TAM was correlated with poor prognosis in patients with nasopharyngeal carcinoma. Peripheral blood mononuclear macrophages after IL-4-induced differentiation of high expression of specific marker CD206, and a large number of secretion of CCL18, identified as type M2 macrophages. Transwell experiments showed that cells co-cultured with M2 macrophages had significantly more cells that migrated and infiltrated into the lower chamber than the control group, with significant difference (P <0.05). Conclusion The infiltration of tumor-associated macrophages is associated with the poor prognosis of NPC. Tumor-associated macrophages may increase the invasion and migration of NPC cells, which may be one of the mechanisms of NPC metastasis.