肿瘤转移是导致癌症患者死亡的主要原因，转移前微环境的形成对肿瘤转移至关重要。然而，转移前微环境如何影响肝癌肺转移尚不清楚。我们发现：形成肺转移前微环境显著促进肝癌肺转移；IL-1β是转移前微环境促进肝癌肺转移的关键分子；敲除肿瘤细胞中IL1R1和IL1R2分别促进和抑制肝癌肺转移；IL1R2在肝癌中表达随病理分级的增加而增加；荷瘤小鼠肺组织培养上清和IL-1β显著增强肝癌细胞粘附能力。据此提出假说：肺转移前微环境中IL-1β通过与经典认知不同的IL1R2通路增强肝癌细胞粘附能力并促进肝癌肺转移，而IL1R1竞争性抑制IL1R2的功能。我们拟结合临床标本、荷瘤小鼠、分子及细胞实验，检测IL1R1/2表达与肝癌患者预后的关系、挖掘新的IL-1β/IL1R2信号通路、阐明肺转移前微环境中IL-1β通过增强肝癌细胞粘附能力促进肝癌肺转移的分子机制，为肝癌肺转移治疗提供新的靶点和理论依据。

Metastasis is the leading cause of death in cancer patients and the premetastatic niche is very important for tumor metastasis. However, it is not clear how the premetastatic niche affects pulmonary metastasis of hepatocellular carcinoma (HCC). We found that the formation of premetastatic niche dramatically enhanced HCC metastasis to the lung. By using RNA-Seq and Il1b-/- mice, IL-1β was identified as a key cytokine in the premetastatic niche that enhanced HCC metastasis to the lung. Pulmonary metastasis was increased in mice bearing IL1R1 knockout tumor cells and decreased in mice bearing IL1R2 knockout tumor cells, respectively. The expression of IL1R2 was significantly up-regulated in HCC and increased with increasing histologic grade. Both lung conditioned medium (LCM) from tumor bearing mice and IL-1β enhanced tumor cell adhesion in vitro. Therefore, we hypothesized that IL-1β in the premetastatic niche enhanced adhesion of tumor cells to the vessel and promoted HCC metastasis to the lung by activating a novel IL1R2 signaling pathway, while IL1R1 competitively inhibited the function of IL1R2. Based on these preliminary results, we planned to combine clinical samples, tumor-bearing mouse models, and molecular and cell experiments to detect the relationship between IL1R1/2 expression and prognosis of HCC patients, to explore the novel IL-1β/IL1R2 signaling pathway, and to clarify the molecular mechanism of IL-1β in the premetastatic niche in promoting pulmonary metastasis of HCC by enhancing tumor cell adhesion. Our findings will provide novel targets and theoretical basis for the treatment of pulmonary metastasis of HCC.