Interleukin-6 promotes the epithelial mesenchymal transition in canine tonsillar squamous cell carcinoma cells

IF 2.2 3区 农林科学 Q1 VETERINARY SCIENCES Research in veterinary science Pub Date : 2025-02-01 DOI:10.1016/j.rvsc.2024.105487
Shunsuke Noguchi , Ryo Shimonishi
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Abstract

Canine oral squamous cell carcinoma (CoSCC) is often associated with suppurative inflammation. Metastasis of malignant tumors is one of the signs of major interest in oncology because it speaks of disease progression, where the involvement of interleukin-6 (IL-6) in cancer progression is so far unknown. Therefore, the aim of this study was the determination of the role of IL-6 in metastasis in CoSCC cells model through expression analysis of mRNA and protein using real-time PCR and western blotting and assessment of cell migration and invasion. The messenger RNA (mRNA) expression level of IL-6 was elevated in CoSCC tissues, and the IL-6 receptor protein was expressed in CoSCC cell lines. Furthermore, IL-6 levels were associated and showed negative correlation with survival time (rs = −0.92857) in dogs with tonsillar SCC. Recombinant canine IL-6 (rcIL-6) treatment promoted migration and invasion, in addition to increasing the viable cell number of the tonsillar SCC cell line (TSCCLN#6). Consistently, the protein expression of phosphorylated ERK1/2 and STAT3 and Fascin1 (FSCN1) was upregulated by treatment with rcIL-6 in a dose-dependent manner. Treatment with ERK or STAT3 inhibitors abolished the effects of rcIL-6, and the ERK inhibitor successfully downregulated the expression of FSCN1. In conclusion, IL-6 may be involved in tonsillar CoSCC invasion and metastasis through the activation of the mitogen-activated protein kinase and Janus tyrosine kinase/signal transducer and activator of transcription signaling.
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白细胞介素-6促进犬扁桃体鳞状细胞癌细胞上皮间质转化。
犬口腔鳞状细胞癌(CoSCC)通常与化脓性炎症有关。恶性肿瘤的转移是肿瘤学的主要兴趣之一,因为它说明了疾病的进展,其中白介素-6 (IL-6)在癌症进展中的参与迄今尚不清楚。因此,本研究的目的是通过real-time PCR和western blotting分析mRNA和蛋白的表达,评估细胞迁移和侵袭,确定IL-6在CoSCC细胞模型转移中的作用。IL-6信使RNA (mRNA)在CoSCC组织中表达水平升高,IL-6受体蛋白在CoSCC细胞系中表达。此外,扁桃体鳞状细胞癌患者IL-6水平与生存时间呈负相关(rs = -0.92857)。重组犬IL-6 (rcIL-6)处理除了增加扁桃体SCC细胞系(tsccln# 6)的活细胞数量外,还促进了迁移和侵袭。与此一致的是,磷酸化的ERK1/2、STAT3和Fascin1 (FSCN1)的蛋白表达在rcIL-6的作用下呈剂量依赖性上调。用ERK或STAT3抑制剂治疗可消除rcIL-6的作用,ERK抑制剂成功下调FSCN1的表达。综上所述,IL-6可能通过激活丝裂原激活蛋白激酶和Janus酪氨酸激酶/信号转导和转录信号激活因子参与扁桃体CoSCC的侵袭转移。
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来源期刊
Research in veterinary science
Research in veterinary science 农林科学-兽医学
CiteScore
4.40
自引率
4.20%
发文量
312
审稿时长
75 days
期刊介绍: Research in Veterinary Science is an International multi-disciplinary journal publishing original articles, reviews and short communications of a high scientific and ethical standard in all aspects of veterinary and biomedical research. The primary aim of the journal is to inform veterinary and biomedical scientists of significant advances in veterinary and related research through prompt publication and dissemination. Secondly, the journal aims to provide a general multi-disciplinary forum for discussion and debate of news and issues concerning veterinary science. Thirdly, to promote the dissemination of knowledge to a broader range of professions, globally. High quality papers on all species of animals are considered, particularly those considered to be of high scientific importance and originality, and with interdisciplinary interest. The journal encourages papers providing results that have clear implications for understanding disease pathogenesis and for the development of control measures or treatments, as well as those dealing with a comparative biomedical approach, which represents a substantial improvement to animal and human health. Studies without a robust scientific hypothesis or that are preliminary, or of weak originality, as well as negative results, are not appropriate for the journal. Furthermore, observational approaches, case studies or field reports lacking an advancement in general knowledge do not fall within the scope of the journal.
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