Enhanced glucose metabolism mediated by CD147 contributes to immunosuppression in hepatocellular carcinoma
Enhanced glucose metabolism mediated by CD147 contributes to immunosuppression in hepatocellular carcinoma
复制标题
CD147介导的葡萄糖代谢增强有助于肝细胞癌的免疫抑制
DOI：
10.1007/s00262-019-02457-y
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发表时间：
2020-04-01
影响因子：
5.8
通讯作者：
Xu, Wengui
中科院分区：
文献类型：
--
作者：
Li, Xiaofeng;Zhang, Yufan;Xu, Wengui
从代谢的角度来看，癌症可以被认为是以重编程的糖酵解代谢为特征的代谢疾病。本研究的目的是研究肝细胞癌（HCC）中CD147介导的葡萄糖代谢调节，及其对肿瘤微环境中免疫反应改变的贡献。建立了几种HCC细胞系和相应的裸鼠异种移植模型，这些模型在CD147表达式中有所不同，以直接研究CD147在葡萄糖代谢重编程中的作用，并确定基本的分子机制。免疫组织化学（IHC）分析和流式细胞仪用于确定HCC中重编程的糖酵解与免疫抑制之间的关系。发现上调的CD147表达式与HCC肿瘤组织中GLUT1，MCT1的表达相关。 CD147通过PI3K/AKT/MTOR信号通路在体外促进了HCC细胞系中的糖酵解代谢。在HCC组织中，免疫抑制淋巴细胞的渗透和CD147表达之间存在正相关。在体外用乳酸刺激下诱导表达FOXP3调控T细胞的积累。总之，CD147通过PI3K/AKT/MTOR信号通路促进了HCC中的糖酵解代谢，并且与HCC中的免疫抑制有关。
From a metabolic perspective, cancer may be considered as a metabolic disease characterized by reprogrammed glycolytic metabolism. The aim of the present study was to investigate CD147-mediated glucose metabolic regulation in hepatocellular carcinoma (HCC) and its contribution to altered immune responses in the tumor microenvironment. Several HCC cell lines and corresponding nude mice xenografts models differing in CD147 expressions were established to directly investigate the role of CD147 in the reprogramming of glucose metabolism, and to determine the underlying molecular mechanisms. Immunohistochemistry (IHC) analyses and flow cytometry were used to identify the relationship between reprogrammed glycolysis and immunosuppression in HCC. Upregulated CD147 expressions were found to be associated with enhanced expressions of GLUT1, MCT1 in HCC tumorous tissues. CD147 promoted the glycolytic metabolism in HCC cell lines in vitro via the PI3K/Akt/mTOR signaling pathway. A positive correlation existed between a profile of immunosuppressive lymphocytes infiltration and CD147 expression in HCC tissues. Accumulation of FOXP3-expressing regulatory T cells was induced under a stimulation with lactate in vitro. In conclusion, CD147 promoted glycolytic metabolism in HCC via the PI3K/Akt/mTOR signaling pathway, and was related to immunosuppression in HCC.