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TREM-1, an Inflammatory Modulator, is Expressed in Hepatocellular Carcinoma Cells and Significantly Promotes Tumor Progression

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Triggering 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.

Methods

Western 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.

Results

TREM-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).

Conclusions

TREM-1 was found to be expressed in HCC cells and to be a prognostic factor for the clinical outcome of HCC.

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Acknowledgment

Financial support by the Major Program of NSFC (No. 81030038), National Key Sci-Tech Project (2012ZX10002011), National Natural Science Foundation of China (Nos. 81272730,81272725, 81372648), FANEDD (No. 201183), Shanghai “Promising Youth Medical Worker” Project (No. 13Y055), and the Fok Ying-Tong Education Foundation (No. 132029). This work was supported by the Major Program of NSFC (No. 81030038), National Key Sci-Tech Project (2012ZX10002011), National Natural Science Foundation of China (Nos. 81272730, 81272725, 81372648), FANEDD (No. 201183), Shanghai “Promising Youth Medical Worker” Project (No. 13Y055), and the Fok Ying-Tong Education Foundation (No. 132029).

Disclosure

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Authors and Affiliations

  1. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China

    Meng Duan MD, Zhi-Chao Wang MD, Xiao-Ying Wang MD, PhD, Jie-Yi Shi MD, PhD, Liu-Xiao Yang MD, Zhen-Bing Ding MD, PhD, Qiang Gao MD, PhD, Jian Zhou MD, PhD & Jia Fan MD, PhD

  2. Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, People’s Republic of China

    Meng Duan MD, Zhi-Chao Wang MD, Xiao-Ying Wang MD, PhD, Jie-Yi Shi MD, PhD, Liu-Xiao Yang MD, Zhen-Bing Ding MD, PhD, Qiang Gao MD, PhD, Jian Zhou MD, PhD & Jia Fan MD, PhD

  3. Institute of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China

    Jian Zhou MD, PhD & Jia Fan MD, PhD

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  1. Meng Duan MD
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  2. Zhi-Chao Wang MD
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Correspondence to Qiang Gao MD, PhD or Jia Fan MD, PhD.

Additional information

Meng Duan, Zhi-Chao Wang, and Xiao-Ying Wang have contributed equally to this work.

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Duan, M., Wang, ZC., Wang, XY. et al. TREM-1, an Inflammatory Modulator, is Expressed in Hepatocellular Carcinoma Cells and Significantly Promotes Tumor Progression. Ann Surg Oncol 22, 3121–3129 (2015). https://doi.org/10.1245/s10434-014-4191-7

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  • DOI: https://doi.org/10.1245/s10434-014-4191-7

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