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    Home > Active Ingredient News > Digestive System Information > Research reveals a new mechanism of hepatitis B virus-induced vascular metastasis and immune escape of liver cancer

    Research reveals a new mechanism of hepatitis B virus-induced vascular metastasis and immune escape of liver cancer

    • Last Update: 2021-03-22
    • Source: Internet
    • Author: User
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    Recently, researcher Yang Pengyuan's research group and researcher Wang Fan's research group of the Institute of Biophysics of the Chinese Academy of Sciences have collaborated on Cancer Research and published a research paper entitled Hepatitis B-induced IL-8 Promotes Hepatocellular Carcinoma Venous Metastasis and Intrahepatic Treg Accumulation.

    The study described the molecular mechanism of HBx inducing the expression of chemokine IL-8 in hepatitis B virus (HBV) infection, promoting the vascular metastasis of liver cancer and the infiltration of regulatory T cells (Treg) in the liver, and providing information for the prevention and treatment of HBV-related liver cancer.
    New theoretical basis and intervention strategies have been established.

    HBV infection is the main cause of liver cancer.
    Clinical studies have shown that HBV-positive liver cancer is often accompanied by vascular metastasis and formation of tumor thrombus (PVTT) in the portal vein, resulting in a poor prognosis for patients.

    However, it is not clear in the academic circles how HBV infection induces vascular metastasis of liver cancer and the mechanism of portal vein tumor thrombosis.

    In this study, the researchers found IL-8, an inflammatory factor regulated by HBV, by screening the cytokine/chemokine array, and verified it in a variety of HBV infection models.

    Signal mechanism studies have shown that the HBV-encoded protein HBx induces the production of IL-8 through the activation of the MEK-ERK signaling pathway.
    IL-8 acts together with its receptor CXCR1 to reduce the tight junctions of vascular endothelial cells and increase the permeability.

    To this end, the researchers constructed transgenic mice expressing human CXCR1 specifically in mouse endothelial cells to study the effect of IL-8-CXCR1 signaling on tumor vascular metastasis in vivo.

    In vivo experiments in which the overexpression of IL-8 in tumor cells activates the IL-8-CXCR1 signal axis found that CXCR1 activation can significantly and specifically enhance the liver metastasis of cancer cells, but it can no longer enhance lung metastasis.

    Further mechanism studies have shown that the IL-8-CXCR1 signal axis enhances the expression of GARP in hepatic sinusoidal endothelial cells, thereby stabilizing Latent-TGF-β anchored on the membrane surface.
    This mechanism promotes the activation of Treg cells by hepatic sinusoidal endothelial cells.
    Induction of differentiation, causing immune escape in the cancer liver.

    This study reveals the HBV-related HBx/IL-8/CXCR1/TGF-β signal cascade, which induces the accumulation of Treg cells in the liver and enhances the vascular metastasis of liver cancer, providing a new theoretical basis and intervention for the prevention and treatment of HBV-related liver cancer Strategy.

    The research was completed by the Institute of Biophysics, University of Science and Technology of China, Eastern Hepatobiliary Surgery Hospital of Naval Military Medical University, and Weill Cornell Medical College.

    Yang Pengyuan and Wang Fan are the co-corresponding authors of the paper, Zhang Changlu, a PhD student jointly trained by the University of Science and Technology of China and the Institute of Biophysics, Gao Yanan, associate researcher in the Yang Pengyuan group of the Institute of Biophysics, Du Chengzhi, a doctoral student in the Wang Fan group, and Geoffrey, PhD student in the Weill Cornell School of Medicine J.
    Markowitz and Fu Jing, PhD from Eastern Hepatobiliary Surgery Hospital of Naval Military Medical University, are the co-first authors of the paper.

    The research work is supported by the National Natural Science Foundation of China and the Chinese Academy of Sciences.

    HBx-IL-8-CXCR1 signal axis promotes vascular metastasis and immune escape mode of HBV-positive liver cancer.
    Source: Institute of Biophysics, Chinese Academy of Sciences
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