单位：[1]Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100730, China.医技科室病理科病理科首都医科大学附属北京友谊医院[2]Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology, Beijing 100730, China.首都医科大学附属同仁医院
Background. Receptor for advanced glycation end products (RAGE) is implicated in tumor biology. Released high mobility group box protein 1 (HMGB1) ligand binding to RAGE receptor in tumor cells promotes tumor progression. The mechanisms of HMGB1-RAGE signaling in M2 macrophages involved in lymphangiogenesis in laryngeal carcinoma remain poorly understood. Here, we assessed the effect of HMGB1-RAGE signaling on M2 macrophages in lymphangiogenesis. Methods. HMGB1, CD163, and D2-40 in laryngeal squamous cell carcinoma (LSCC, n=123), laryngeal precursor lesions (LPLs, n=102), and vocal polyp (VP, n=55) were analyzed by immunohistochemistry. THP-1 cell-expressed RAGE gene was knocked down and then polarized to M0 macrophages and M2 macrophages. IL-23, TNF-alpha, TGF-beta, and IL-10 were measured by ELISA; IL-1 beta, IL-12, IL-10, and CCL-13 were evaluated by RT-qPCR, and CD206, CD163, and RAGE were evaluated by western blot to evaluate whether classical M2 macrophages were obtained. Conditioned media from RAGE(+/-) M0 macrophages and RAGE(+/-) M2 macrophages incubated in the presence or absence of HMGB1, anti-Toll-like receptor (TLR)2, anti-TLR4 antibodies, and anti-VEGF-C antibodies were collected separately for human dermal lymphatic endothelial cells (HDLEC) for proliferation, migration, lymphangiogenesis assay, and VEGF-C concentration analysis. Results. HMGB1 and M2 macrophage densities were increased in LSCC (P < 0.01). HMGB1 and M2 macrophage densities were significantly correlated with lymphatic vessel density (LVD) in LSCC (P < 0.01). The HMGB1 overexpression and higher M2 macrophage density were involved in lymph node metastasis (P < 0.01) and poor prognosis (P < 0.05). In vitro, conditioned medium from HMGB1-stimulated RAGE(+) M2 macrophages activated lymphangiogenesis by upregulating the VEGF compared to controls (P < 0.05). On the contrary, RAGE knockdown obviously decreased the corresponding effects of HMGB1-preconditioned M2 macrophages upon HDLEC (P < 0.05). HMGB1-TLR pathway does not significantly increase HDLEC proliferation, migration, and lymphangiogenesis on M2 macrophages. Conclusions. HMGB1 promotes lymphangiogenesis by activation of RAGE on M2 macrophages. Targeting RAGE may provide an effective therapeutic strategy against M2 macrophages in LSCC patients with lymph node metastasis.
基金：
Beijing Municipal Education Commission [KZ201910025033]
语种：
外文
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|4 区医学
小类|4 区生物工程与应用微生物4 区遗传学4 区医学：研究与实验4 区病理学
最新[2025]版：
无
JCR分区：
出版当年[2020]版：
Q2BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ2PATHOLOGYQ2GENETICS & HEREDITYQ3MEDICINE, RESEARCH & EXPERIMENTAL
第一作者单位：[1]Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100730, China.
通讯作者：
推荐引用方式(GB/T 7714)：
Su Caili,Jia Shuangshuang,Ma Zhihong,et al.HMGB1 Promotes Lymphangiogenesis through the Activation of RAGE on M2 Macrophages in Laryngeal Squamous Cell Carcinoma[J].DISEASE MARKERS.2022,2022:doi:10.1155/2022/4487435.
APA：
Su Caili,Jia Shuangshuang,Ma Zhihong,Zhang Hong,Wei Li&Liu Honggang.(2022).HMGB1 Promotes Lymphangiogenesis through the Activation of RAGE on M2 Macrophages in Laryngeal Squamous Cell Carcinoma.DISEASE MARKERS,2022,
MLA：
Su Caili,et al."HMGB1 Promotes Lymphangiogenesis through the Activation of RAGE on M2 Macrophages in Laryngeal Squamous Cell Carcinoma".DISEASE MARKERS 2022.(2022)
