IL-8诱导的肿瘤相关巨噬细胞对肝细胞肝癌侵袭转移的影响

  目的  探究外源性IL-8对单核细胞的活化作用及IL-8活化后的肿瘤相关巨噬细胞（tumor-associated macrophages，TAMs）对肝细胞肝癌（hepatocellular carcinoma，HCC）侵袭转移的影响。  方法  外源性IL-8刺激THP-1细胞后检测M1、M2型TAMs的比例。IL-8活化的TAMs与HCC细胞共孵育，利用RT-PCR和Western blot法检测TAMs对HCC细胞上皮间质转化（epithelial-mesenchymal transition，EMT）的影响；利用划痕修复实验和Transwell侵袭实验探究TAMs对HCC细胞侵袭转移的影响；并在100例HCC样本中进行组织水平验证。  结果  外源性IL-8可诱导THP-1细胞的表型向M2型TAMs方向分化。IL-8体外诱导的TAMs可以反作用于HCC，促使其发生EMT，进而促进其侵袭转移。在HCC组织中证实IL-8与TAMs浸润呈明显的正相关（r=0.22，P < 0.05），同时浸润的TAMs与神经细胞型钙黏蛋白（N-cadherin）的表达量呈正相关（r=0.20，P < 0.05）。  结论  在HCC中，IL-8可以趋化TAMs浸润并促进其活化，活化后的TAMs可促进HCC细胞EMT和侵袭转移。 

The effects of IL-8-activated tumor-associated macrophages on hepatocellular carcinoma invasion and metastasis

  Objective  To study the effects of IL-8 on the polarization of monocytes and the effects of IL-8-induced tumor-associated macrophages (TAMs) on the invasion and metastasis of hepatocellular carcinoma (HCC).  Methods  After exogenous IL-8 stimulation of THP-1 cells for 72h, the percentages of M1 and M2 TAMs were examined. RT-PCR and Western blot assays were used to study epithelial-mesenchymal transition (EMT), and wound-healing and transwell assays were preformed to study the invasion potential of HCC cells after co-culturing with TAMs and HCC cell lines in vitro. Lastly, 100 cases of HCC tissue samples were used to validate the correlation among TAM numbers, IL-8, and EMT features of HCC cells via immunohistochemistry (IHC) staining methods.  Results  Exogenous IL-8 induced significant M2 polarization of TAMs in THP-1 cells. TAMs further promoted EMT in HCC and enhanced the invasion potential of HCC in vitro. Finally, significant positive correlations among the numbers of TAMs, IL-8 expression, and N-cadherin expression were identified in primary HCC tissue samples (r=0.22, r=0.20, P < 0.05).  Conclusions  IL-8 locally attracted and activated TAMs, and promoted M2 polarization of TAMs, which further promoted the EMT and invasion potential of HCC cells both in vitro and in vivo.