Linagliptin's impact on lymphatic barrier and lymphangiogenesis in oral cancer with high glucose.

IF 2.9 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Oral diseases Pub Date : 2024-10-01 Epub Date: 2024-02-20 DOI:10.1111/odi.14893

Hongyu Wang, Xiao She, Qiongdong Xu, Xingyu Zhou, Qinchao Tang, Huakun Wei, Tianjing Huang, Feixin Liang

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Abstract

Objectives: Uncertainties remain regarding the effect of elevated glucose levels on lymphatic metastasis of cancer cells. Our study elucidated the mechanisms linking high glucose to lymphangiogenesis and lymphatic barrier-related factors and investigated the protective role of linagliptin against lymphatic barrier dysfunction.

Materials and methods: A CAL-27-LEC co-culture system was established. Sodium fluorescein permeability assay observed lymphatic endothelial cell permeability. Western blotting and RT-qPCR detected protein and mRNA expression under different conditions, respectively. CCK-8, scratch wound healing, and transwell assays revealed cell migration and proliferation. Tube formation experiment tested capacity for endothelial tube formation. Immunohistochemical staining analyzed tissue sections from 43 oral cancer individuals with/without diabetes.

Results: In high-glucose co-culture system, we observed increased lymphatic barrier permeability and decreased expression of ZO-1 and occludin, two tight-junction proteins; conversely, the expression of PAR2, a high permeability-related protein, was increased. Following linagliptin treatment, the expression levels of VEGF-C, VEGFR-3, and PAR2 decreased, while those of ZO-1 and occludin increased. Considerably higher levels of LYVE-1 expression in individuals with diabetes than in those without diabetes.

Conclusions: By ameliorating the high glucose-induced disruption of the lymphatic endothelial barrier, linagliptin may reduce lymphangiogenesis and exhibit an inhibitory effect on lymphatic metastasis in oral cancer patients with diabetes.

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利拉利汀对高糖口腔癌患者淋巴屏障和淋巴管生成的影响

目的：葡萄糖水平升高对癌细胞淋巴转移的影响仍存在不确定性。我们的研究阐明了高血糖与淋巴管生成和淋巴屏障相关因素的联系机制，并研究了利拉利汀对淋巴屏障功能障碍的保护作用：建立了CAL-27-LEC共培养系统。荧光素钠通透性试验观察淋巴内皮细胞的通透性。Western 印迹和 RT-qPCR 分别检测不同条件下蛋白质和 mRNA 的表达。CCK-8、划痕伤口愈合和透孔试验显示了细胞的迁移和增殖。管形成实验检测了内皮管形成的能力。免疫组化染色分析了 43 例患有/未患有糖尿病的口腔癌患者的组织切片：结果：在高糖共培养系统中，我们观察到淋巴屏障通透性增加，ZO-1和闭塞素（两种紧密连接蛋白）的表达减少；相反，高通透性相关蛋白PAR2的表达增加。利拉利汀治疗后，VEGF-C、VEGFR-3 和 PAR2 的表达水平下降，而 ZO-1 和闭塞素的表达水平上升。糖尿病患者的 LYVE-1 表达水平明显高于非糖尿病患者：结论：通过改善高血糖引起的淋巴内皮屏障破坏，利拉利汀可能会减少淋巴管生成，并对糖尿病口腔癌患者的淋巴转移产生抑制作用。

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.