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.
Keywords: ERK1/2; Fascin1; Interleukin-6; Metastasis; STAT3; Squamous cell carcinoma.
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