TREM-1, an Inflammatory Modulator, is Expressed in Hepatocellular Carcinoma Cells and Significantly Promotes Tumor Progression
TREM-1, an Inflammatory Modulator, is Expressed in Hepatocellular Carcinoma Cells and Significantly Promotes Tumor Progression
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TREM-1 是一种炎症调节剂，在肝细胞癌细胞中表达并显着促进肿瘤进展
DOI：
10.1245/s10434-014-4191-7
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发表时间：
2015-09-01
影响因子：
3.7
通讯作者：
Fan, Jia
中科院分区：
文献类型：
--
作者：
Duan, Meng;Wang, Zhi-Chao;Fan, Jia
背景髓样细胞触发受体1（TREM-1）是一种新的调节炎症反应的分子。肝细胞癌（HCC）是一种众所周知的炎症相关癌症。然而，TREM-1的表达及其对HCC细胞的直接影响尚未确定。MethodsWestern印迹，定量逆转录-PCR（qRT-PCR），和免疫荧光法检测TREM-1的表达。通过pcDNA（具有CMV启动子的哺乳动物表达载体）上调TREM-1和通过shRNA（短发夹RNA）下调TREM-1用于确定该分子的功能。采用Transwell法、CCK-8法、细胞周期法和细胞凋亡法检测TREM-1对肝癌细胞的作用。结果TREM-1蛋白在肝癌细胞和肿瘤组织中均有表达，且与肿瘤的预后密切相关。功能实验表明，TREM-1显着促进肝癌细胞的增殖，侵袭，并抑制凋亡。在TREM-1上调或下调下的炎性细胞因子谱表明大多数促炎细胞因子与TREM-1表达显著正相关，包括IL-1β、TNF-α和MCP-1。Western blot分析显示，p65、STAT 3、ERK和AKT可能是TREM-1信号转导的下游效应子。TREM-1的高表达与肝癌患者的复发率和生存率显著相关，是肝癌复发的独立预后因素（P= 0.009）。
BackgroundTriggering receptors expressed on myeloid cells 1 (TREM-1) is a novel molecule that modulates inflammatory responses. Hepatocellular carcinoma (HCC) is a well-known type of inflammation-related cancer. However, TREM-1 expression and its direct effects on HCC cells have not been previously determined.MethodsWestern blotting, quantitative reverse transcription-PCR (qRT-PCR), and immunofluorescence were used to detect TREM-1 expression. TREM-1 upregulation by pcDNA (mammalian expression vector with the CMV promoter) and its downregulation by shRNA (short hairpin RNA) were used to determine the function of this molecule. Transwell, CCK-8, cell cycle, and apoptosis assays were used to detect the effects of TREM-1 on HCC cells. Immunohistochemical staining of samples from a cohort of 322 HCC patients was used to determine the prognostic value of TREM-1.ResultsTREM-1 investigation through Western blot, qRT-PCR, and immunofluorescence analyses revealed that TREM-1 was expressed in HCC cells and tumor tissues. Functional experiments suggested that TREM-1 significantly promoted proliferation, invasion, and inhibited apoptosis of HCC cells. Inflammatory cytokine profiles under TREM-1 up- or downregulation indicated the majority of proinflammation cytokines significantly and positively correlated with TREM-1 expression, including IL-1β, TNF-α, and MCP-1. Western blot analyses revealed that p65, STAT3, ERK, and AKT might be the downstream effectors of TREM-1 signal transduction. High TREM-1 expression correlated significantly with increased recurrence and poorer survival in HCC patients, and it was an independent prognostic factor for recurrence (P= 0.009).ConclusionsTREM-1 was found to be expressed in HCC cells and to be a prognostic factor for the clinical outcome of HCC.