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Targeting of Annexin A1 in Tumor-associated Macrophages as a therapeutic strategy for hepatocellular carcinoma

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资源类型：
Pubmed体系：
作者：
Song Zhenghui[1,2,3,4] * ; Wang Xue[4,5] ; Liu Xinhui[4,5] ; Luo Yue[4,5] ; Qiu Jieya[1,2,3] ; Yin Aiqi[6] ; Liu Yun[7] ; Yi Hong[1,2,3] ; Xiao Zhiqiang[1,2,3,*2] ; Li Aimin[4,5,*1] ;
机构： [1]Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China [2]Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha 410008, China [3]National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China [4]Department of Hepatology, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, China [5]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China [6]Department of Obstetrics, Shenzhen Maternity and Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong 518028, China [7]Department of Endocrinology and Metabolic Diseases, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou 423000, China
出处：
DOI： 10.1016/j.bcp.2023.115612
ISSN：

关键词： Annexin A1 Ac2-26 hrANXA1 Tumor-associated Macrophages Hepatocellular Carcinoma Tumor microenvironment

摘要：
Hepatocellular carcinoma (HCC) is a common aggressive, malignant tumor with limited treatment options. Currently, immunotherapies have low success rates in the treatment of HCC. Annexin A1 (ANXA1) is a protein related to inflammation, immunity and tumorigenesis. However, the role of ANXA1 in liver tumorigenesis remains unknown. Therefore, we sought to explore the feasibility of ANXA1 as a therapeutic target for HCC. Here, we analyzed ANXA1 expression and localization by HCC microarray and immunofluorescence experiments. Using an in vitro culture system, monocytic cell lines and primary macrophages were employed to investigate the biological functions of cocultured HCC cells and cocultured T cells. In vivo, Ac2-26, human recombinant ANXA1 (hrANXA1), and cell depletion (macrophages or CD8 + T cells) experiments were further conducted to investigate the role of ANXA1 in the tumor microenvironment (TME). We found that ANXA1 was overexpressed in mesenchymal cells, especially macrophages, in human liver cancer. Moreover, the expression of ANXA1 in mesenchymal cells was positively correlated with programmed death-ligand 1 expression. Knockdown of ANXA1 expression inhibited HCC cell proliferation and migration by increasing the M1/M2 macrophage ratio and promoting T-cell activation. hrANXA1 promoted malignant growth and metastasis in mice by increasing the infiltration and M2 polarization of tumor-associated macrophages (TAMs), generating an immunosuppressive TME and suppressing the antitumor CD8 + T-cell response. Together, our findings reveal that ANXA1 may be an independent prognostic factor for HCC and demonstrate the clinical translational significance of ANXA1 for tumor immunotherapy in HCC.Copyright © 2023. Published by Elsevier Inc.

基金：
The authors would like to thank Qianbing Zhang for the analysis and technical support of flow cytometry. This work was supported by the following research grants: National Natural Science Foundation of China (Nos. 82203074 and 82170552); Natural Science Foundation of Guangdong Province (No. 2022A1515012620); Natural Science Foundation of Hunan Province (No. 2021JJ31120); Department of Education of Guangdong Province (No. 2022KTSCX023); Scientific Research Fund of Hunan Provincial Education Department (No. 21A0008); Scientific Research Fund of Hunan Provincial Health Commission (No. D202303068727); President’s Fund of Integrated Hospital of Traditional Chinese Medicine (No. 1202103008).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类 | 2 区 医学
小类 | 2 区 药学
最新[2025]版：
大类 | 2 区 医学
小类 | 2 区 药学
第一作者：
第一作者机构： [1]Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China [2]Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha 410008, China [3]National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China [4]Department of Hepatology, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, China
通讯作者：
通讯机构： [1]Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China [2]Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha 410008, China [3]National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China [4]Department of Hepatology, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, China [5]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China [*1]Department of Hepatology, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, No.13 Shiliugang Road, Guangzhou, Guangdong 510315, China [*2]Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China
推荐引用方式(GB/T 7714)：
Song Zhenghui,Wang Xue,Liu Xinhui,et al.Targeting of Annexin A1 in Tumor-associated Macrophages as a therapeutic strategy for hepatocellular carcinoma[J].Biochemical pharmacology.2023,213:115612.doi:10.1016/j.bcp.2023.115612.
APA：
Song Zhenghui,Wang Xue,Liu Xinhui,Luo Yue,Qiu Jieya...&Li Aimin.(2023).Targeting of Annexin A1 in Tumor-associated Macrophages as a therapeutic strategy for hepatocellular carcinoma.Biochemical pharmacology,213,
MLA：
Song Zhenghui,et al."Targeting of Annexin A1 in Tumor-associated Macrophages as a therapeutic strategy for hepatocellular carcinoma".Biochemical pharmacology 213.(2023):115612

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