肝癌介入栓塞后局部缺氧引起的炎症反应与转移和复发有密切关系。本课题前期研究发现缺氧诱导肝癌细胞发生上皮间质转化，预实验显示缺氧引起肝癌细胞分泌HMGB1，基于炎性因子HMGB1可以活化Kupffer细胞（KCs），参与多种肝脏疾病的发生发展过程。因此本课题提出“HMGB1介导肝癌细胞与KCs的交叉对话影响肝癌转移”的设想，拟用体外细胞共培养、趋化及干预实验，通过ELISA、Western blot和PCR等技术研究肝癌细胞在缺氧条件下释放的HMGB1对KCs的活化，以及活化的KCs分泌的HMGB1对肝癌细胞侵袭转移能力的影响，明确TLR4/NF-κB信号通路调节KCs和肝癌细胞的交叉对话的作用。另外通过肝癌动物模型，验证介入栓塞联合HMGB1抑制，对KCs活化和肝癌转移的抑制效果。以期为临床寻找抑制肝癌侵袭和转移的治疗靶点，提高肝癌介入栓塞的疗效。

The local recurrence after transarterial chemoembolization (TACE) always occur at the margin of tumor, because of inflammation developed after hypoxia which lead to iodine-oil cleaning up. The hypoxia after embolization is important to Kupffer cells activation and recruiting. In our priliminary study, we identified that hypoxia could be induced after embolization, which could not only stimulate hepatocellular carcinoma (HCC) cell motility, but also induce epithelial-mesenchymal transition, resulting in HCC progression. In pre-experiment, we also found that high mobility group protein 1 (HMGB1) is secreted higher by HCC in hypoxia. HMGB1 play a role as inflammatory cytokine, which could activate Kupffer cells and involved in lots of hepatic disease, such as hepatic ischemia- reperfusion injury, hepatic fibrosis. Based on the above information, in this study, we will elucidate the cross-talk between Kupffer cell and hepatoma and its significance in HCC recurrence and metastasis after embolization. Using coculture analysis, specific chemotractant models and mice experiments for intervention, we will emphsis on the biological roles and the underly mechanisms of the HMGB1 in modulating the Kupffer cell and hepatoma, which in turn leading tumor progress in hypoxia microenvironment. In addtion, our study will also investigate the effect and the associated molecullar mechnisms of HMGB1 on HCC cell invasion and metastasis, which could be response to the activation of TLR4/NF-κB signal pathway. Modulating HMGB1 or Kupffer cell will repress the invasive potential of HCC cells, and leading to reduced HCC recurrence and improve survival.