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中性粒细胞调控口腔鳞状细胞癌的肿瘤血管生成及其趋化素的作用

Neutrophils regulate tumor angiogenesis in oral squamous cell carcinoma and the role of Chemerin.

机构信息

Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao city, Shandong Province, China.

Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, Qingdao city, Shandong Province, China.

出版信息

Int Immunopharmacol. 2023 Aug;121:110540. doi: 10.1016/j.intimp.2023.110540. Epub 2023 Jun 22.

Abstract

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity. Tumor angiogenesis plays a crucial role in tumor progression. Studies have established the correlation between neutrophils and tumor angiogenesis in the tumor microenvironment. A previous study found that overexpression of Chemerin- in OSCC increased the infiltration of neutrophils in tumor tissues. This study aims to investigate the mechanisms underlying the regulation of the development and progression of OSCC, which have great significance in enhancing the postoperative survival of patients with OSCC. This study evaluated the accuracy of neutrophil count combined with MVD in predicting patients' survival time and its relationship with clinicopathological parameters and prognosis. Additionally, the study explored the effects of the Chemerin-neutrophil interaction on the angiogenic function of HUVECs. In OSCC, the overexpression of Chemerin promoted the angiogenesis of HUVECs through neutrophils. Moreover, Chemerin upregulated pro-angiogenic factors (e.g., VEGF-A, MMP-9, MMP-2, and S100A9) in neutrophils by activating MEK/ERK signaling pathway. In vivo experiments demonstrated that Chemerin may promote tumor growth by regulating tumor angiogenesis. In conclusion, the results suggest that neutrophil count and MVD serve as poor prognostic factors for patients with OSCC, and their combination is a more effective factor in predicting the survival time of OSCC patients. Neutrophils potentially contribute to angiogenesis through MEK/ERK signaling pathway via Chemerin and participate in the progression and metastasis of OSCC.

摘要

口腔鳞状细胞癌(OSCC)是口腔最常见的恶性肿瘤。肿瘤血管生成在肿瘤进展中起着至关重要的作用。研究已经确立了肿瘤微环境中中性粒细胞与肿瘤血管生成之间的相关性。先前的一项研究发现,Chemerin 在 OSCC 中的过度表达增加了肿瘤组织中中性粒细胞的浸润。本研究旨在探讨 Chemerin 调节 OSCC 发展和进展的机制,这对于提高 OSCC 患者的术后生存率具有重要意义。本研究评估了中性粒细胞计数与 MVD 联合预测患者生存时间的准确性及其与临床病理参数和预后的关系。此外,该研究还探讨了 Chemerin-中性粒细胞相互作用对 HUVEC 血管生成功能的影响。在 OSCC 中,Chemerin 的过表达通过中性粒细胞促进 HUVEC 的血管生成。此外,Chemerin 通过激活 MEK/ERK 信号通路在上皮细胞中上调促血管生成因子(如 VEGF-A、MMP-9、MMP-2 和 S100A9)。体内实验表明,Chemerin 可能通过调节肿瘤血管生成促进肿瘤生长。总之,研究结果表明,中性粒细胞计数和 MVD 是 OSCC 患者预后不良的因素,两者的联合是预测 OSCC 患者生存时间的更有效因素。中性粒细胞可能通过 Chemerin 激活 MEK/ERK 信号通路促进血管生成,并参与 OSCC 的进展和转移。

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