ALDH3A1 upregulation inhibits neutrophils N2 polarization and halts oral cancer growth.

IF 2.9 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Oral diseases Pub Date : 2024-10-01 Epub Date: 2024-01-15 DOI:10.1111/odi.14863

Ying He, Yi Qu, Shan Jin, Yongfeng Zhang, Lizheng Qin

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引用次数: 0

Abstract

Objectives: Tumor-associated neutrophils (TANs) are among the most abundant inflammatory cells in tumor microenvironment (TME). Aldehyde dehydrogenase 3A1 (ALDH3A1) is significantly reduced in oral squamous cell carcinoma (OSCC), ALDH3A1 overexpression suppresses tumorigenesis by inhibiting inflammation. This study investigated the relationship and mechanisms underlying the crosstalk between ALDH3A1 and TANs in OSCC.

Materials and methods: Immunohistochemistry and immunofluorescence were performed to investigate the abundance of TANs and the expression of ALDH3A1. dHL-60 were induced with tumor-conditioned media and recombinant IL-6/IL-8. The expression of key proteins in PI3K/AKT/NF-κB pathway were detected by RT-PCR and western blot. A xenograft model was utilized to examine the effect of ALDH3A1 on tumorigenicity and polarization of TANs.

Results: In patients with OSCC, TANs significantly increased and were associated with a worse prognosis. Additionally, ALDH3A1 negatively correlated with TANs infiltration and especially the N2 phenotype which was the prominent part in OSCC. Furthermore, our study demonstrated that tumor-derived IL-8 drives ALDH3A1-mediated TANs N2 polarization in the TME through PI3K/AKT/NF-κB pathway in vitro and in vivo.

Conclusion: Our results indicate that TANs can serve as a prognostic biomarker and ALDH3A1 could be a promising therapeutic target for regulating TANs N2 polarization in antitumor therapy.

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ALDH3A1上调可抑制中性粒细胞的N2极化并阻止口腔癌的生长。

目的：肿瘤相关中性粒细胞（TANs）是肿瘤微环境（TME）中最丰富的炎症细胞之一。口腔鳞状细胞癌（OSCC）中的醛脱氢酶 3A1（ALDH3A1）明显减少，ALDH3A1 过表达可通过抑制炎症抑制肿瘤发生。本研究探讨了ALDH3A1与TANs在OSCC中相互影响的关系和机制：采用免疫组化和免疫荧光技术研究 TANs 的丰度和 ALDH3A1 的表达。通过RT-PCR和Western blot检测PI3K/AKT/NF-κB通路中关键蛋白的表达。利用异种移植模型研究了ALDH3A1对TANs致瘤性和极化的影响：结果：在 OSCC 患者中，TANs 明显增加，并与预后恶化相关。此外，ALDH3A1 与 TANs 浸润呈负相关，尤其是 N2 表型，这是 OSCC 的主要特征。此外，我们的研究还表明，在体外和体内，肿瘤衍生的IL-8通过PI3K/AKT/NF-κB途径驱动ALDH3A1介导的TME中的TANs N2极化：我们的研究结果表明，TANs可作为一种预后生物标志物，而ALDH3A1则可能是抗肿瘤治疗中调节TANs N2极化的一个有前景的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oral diseases 医学-牙科与口腔外科

CiteScore

7.60

自引率

5.30%

发文量

325

审稿时长

4-8 weeks

期刊介绍： Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.