Oral submucous fibrosis (OSF) involves a high risk of malignant transformation and has been implicated in oral cancer. Limited studies have been conducted on the role of OSF in relation to the invasive capabilities and epithelial-mesenchymal transition (EMT) in oral cancer. Herein, we investigated the effects of OSF on the microenvironment of human oral cancer cells. The results showed that the conditioned medium (CM) of fibrotic buccal mucosal fibroblasts (fBMFs) strongly induced the invasion of oral cancer cells and increased the activities of matrix metalloproteinase-2. OSF significantly induced the EMT in oral cancer cells and downregulated epithelial markers, such as E-cadherin, but significantly elevated vimentin, fibronectin, N-cadherin, RhoA, Rac-1 and FAK. Insulin-like growth factor-1 (IGF-1) was elevated in OSF. The protein levels of the IGF-1R were upregulated specifically in fBMF CM treatment for oral cancer cells, and the IGFR gene was confirmed by The Cancer Genome Atlas patient transcriptome data. The Kaplan-Meier curve analysis revealed that patients with oral squamous cell carcinoma and high IGFR expression levels had poorer 5-year survival than those with low IGFR expression (p = 0.004). The fBMF-stimulated EMT cell model may recapture some of the molecular changes during EMT progression in clinical patients with oral cancer.

中文翻译：

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口腔粘膜下纤维化通过激活MMP-2和IGF-IR刺激口腔鳞状细胞癌的侵袭和上皮间质转化

口腔粘膜下纤维化（OSF）具有很高的恶变风险，并与口腔癌有关。关于 OSF 在口腔癌侵袭能力和上皮间质转化 (EMT) 方面的作用的研究有限。在此，我们研究了 OSF 对人类口腔癌细胞微环境的影响。结果表明，纤维化颊粘膜成纤维细胞（fBMF）的条件培养基（CM）强烈诱导口腔癌细胞的侵袭并增加基质金属蛋白酶-2的活性。OSF显着诱导口腔癌细胞中的EMT并下调上皮标记物，例如E-钙粘蛋白，但显着升高波形蛋白、纤连蛋白、N-钙粘蛋白、RhoA、Rac-1和FAK。OSF 中胰岛素样生长因子-1 (IGF-1) 升高。在口腔癌细胞的 fBMF CM 治疗中，IGF-1R 的蛋白水平特别上调，并且癌症基因组图谱患者转录组数据证实了 IGFR 基因。Kaplan-Meier曲线分析显示，IGFR高表达的口腔鳞状细胞癌患者的5年生存率比IGFR低表达的患者差（p = 0.004）。fBMF 刺激的 EMT 细胞模型可能会重现临床口腔癌患者 EMT 进展过程中的一些分子变化。