TAMs来源的CCL5激活ERK1/2/p38信号通路在口腔鳞癌转移中的作用研究

The study on the role and mechanism of oral squamous cell carcinoma lymph node metastasis regulated by TAMs secreted CCL5 via ERK1/2/p38 signaling pathway

目的本研究旨在探讨CCL5在口腔鳞癌转移中的重要作用机制。方法采用免疫组织化学和免疫荧光染色检测口腔鳞癌肿瘤组织及癌旁组织中CCL5和CD163的表达定位。建立口腔鳞癌细胞系(SCC-9和CAL27)-TAMs共培养体系,同时抑制CCL5及信号分子表达,通过免疫印迹检测EMT标志物,并通过侵袭实验检测肿瘤细胞侵袭能力。结果我们首次利用免疫组织化学法发现,伴有淋巴结转移的OSCC肿瘤组织中CCL5与CD163的共表达显著高于无转移患者,且两者表达显著相关。细胞实验发现,TAMs来源的CCL5能够诱导OSCC细胞的侵袭;ERK1/2/p38信号通路调节的上皮间质转化(EMT)参与了CCL5诱导的OSCC细胞侵袭。结论TAMs来源的CCL5在推动口腔鳞癌细胞EMT及侵袭中起重要作用,本研究为口腔鳞癌转移的治疗提供了潜在的新靶点。

Objective To investigate the important role of CCL5 in the regulation of OSCC metastasis.Methods Immunohistochemical and immunofluorescence staining were used to detect the expression and distribution of CCL5 and CD163 in tumor tissues of OSCC patients.We established OSCC cell(CAL27 and SCC-9)-TAMs co-culture system and inhibited CCL5 and signal factors expression.EMT markers were detected by immunoblotting,and tumor cell invasion ability were detected by transwell system assay.Results We firstly determine that CCL5 and CD163 were highly co-expressed in metastatic tumor tissues,which positively correlated with each other.In vitro study identified that CCL5 secreted by TAMs enhanced OSCC invasion via ERK1/2/p38 signaling pathway induced EMT.Conclusion CCL5 secreted by TAMs plays an important role in promoting EMT and invasion of oral squamous cell carcinoma,and may provide provide a new target for clinical treatment of OSCC lymph node metastasis.