{"title":"Epithelial-mesenchymal transition in oral cancer cells induced by prolonged and persistent Fusobacterium nucleatum stimulation","authors":"","doi":"10.1016/j.job.2024.05.006","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><p>Several studies have reported the effects of <span><span>Fusobacterium nucleatum</span></span><span> stimulation on oral cancer cells. However, given that these studies typically span a stimulation period of three days to eight days, the </span><em>in vitro</em> studies conducted to date may not fully mimic the oral cancer environment, which involves constant exposure to oral commensal bacteria. This study aimed to elucidate the effects of prolonged and persistent <em>Fusobacterium nucleatum</em> infection on oral cancer cells.</p></div><div><h3>Methods</h3><p><span>Human tongue squamous cell carcinoma (SCC) cells were continuously stimulated with </span><em>Fusobacterium nucleatum</em> for two or four weeks, then experimentally evaluated.</p></div><div><h3>Results</h3><p>Prolonged, persistent <em>Fusobacterium nucleatum</em><span> stimulation increased the cells’ proliferative, invasive, and migratory capacities, decreased their expression of epithelial markers, and increased their expression of mesenchymal markers progressively with time. The cells also adopted a spindle-shaped morphology and cell-to-cell contact dependence was progressively lost, suggesting time-dependent occurrence of epithelial-mesenchymal transition. Furthermore, mRNA levels of CD44, a cancer stem cell marker, were time-dependently upregulated. When SCC cells were stimulated with </span><em>Fusobacterium nucleatum</em><span> for four weeks in the presence of dexamethasone, </span><em>Fusobacterium nucleatum</em> induced epithelial-mesenchymal transition was inhibited.</p></div><div><h3>Conclusions</h3><p>Epithelial-mesenchymal transition in human tongue SCC cells was time-dependently induced by prolonged, persistent <em>Fusobacterium nucleatum</em><span><span> stimulation and inhibited by dexamethasone. Routine decontamination of the </span>oral cavity may be crucial for controlling tumor invasion and metastasis.</span></p></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Oral Biosciences","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1349007924000896","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
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Abstract
Objectives
Several studies have reported the effects of Fusobacterium nucleatum stimulation on oral cancer cells. However, given that these studies typically span a stimulation period of three days to eight days, the in vitro studies conducted to date may not fully mimic the oral cancer environment, which involves constant exposure to oral commensal bacteria. This study aimed to elucidate the effects of prolonged and persistent Fusobacterium nucleatum infection on oral cancer cells.
Methods
Human tongue squamous cell carcinoma (SCC) cells were continuously stimulated with Fusobacterium nucleatum for two or four weeks, then experimentally evaluated.
Results
Prolonged, persistent Fusobacterium nucleatum stimulation increased the cells’ proliferative, invasive, and migratory capacities, decreased their expression of epithelial markers, and increased their expression of mesenchymal markers progressively with time. The cells also adopted a spindle-shaped morphology and cell-to-cell contact dependence was progressively lost, suggesting time-dependent occurrence of epithelial-mesenchymal transition. Furthermore, mRNA levels of CD44, a cancer stem cell marker, were time-dependently upregulated. When SCC cells were stimulated with Fusobacterium nucleatum for four weeks in the presence of dexamethasone, Fusobacterium nucleatum induced epithelial-mesenchymal transition was inhibited.
Conclusions
Epithelial-mesenchymal transition in human tongue SCC cells was time-dependently induced by prolonged, persistent Fusobacterium nucleatum stimulation and inhibited by dexamethasone. Routine decontamination of the oral cavity may be crucial for controlling tumor invasion and metastasis.