Published in:
Journal of Oral Pathology & Medicine, 47 (2018) 5, Seite 492-501
Language:
English
DOI:
10.1111/jop.12707
ISSN:
0904-2512;
1600-0714
Origination:
Footnote:
Description:
<jats:sec><jats:title>Aim</jats:title><jats:p>This study aimed to investigate the role of p38 <jats:styled-content style="fixed-case">MAPK</jats:styled-content> in maintenance of cancer stem cell (<jats:styled-content style="fixed-case">CSC</jats:styled-content>) phenotype, therapy resistance, and <jats:styled-content style="fixed-case">DNA</jats:styled-content> damage repair and response in head and neck squamous cell carcinoma (<jats:styled-content style="fixed-case">HNSCC</jats:styled-content>).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In this study, 104 <jats:styled-content style="fixed-case">HNSCC</jats:styled-content> patients were included. Western blot, immunohistochemistry, and <jats:styled-content style="fixed-case">qPCR</jats:styled-content> analysis were performed to investigate the expression level of p‐p38 and <jats:styled-content style="fixed-case">CSC</jats:styled-content> markers in cut margin and tumor area of <jats:styled-content style="fixed-case">HNSCC</jats:styled-content> patients. The expression level of p‐p38 and <jats:styled-content style="fixed-case">CSC</jats:styled-content> markers was also evaluated in <jats:styled-content style="fixed-case">HNSCC</jats:styled-content> cells with or without p38 inhibitor. Chemoresistance, wound healing capacity, and multicellular tumor spheroids (<jats:styled-content style="fixed-case">MCTS</jats:styled-content>) formation capacity were evaluated in <jats:styled-content style="fixed-case">HNSCC</jats:styled-content>‐derived cell lines with or without p38 inhibitor. In addition, <jats:styled-content style="fixed-case">DNA</jats:styled-content> damage response and repair capacities were also evaluated in <jats:styled-content style="fixed-case">HNSCC</jats:styled-content> cells after p38 inhibition using alkaline comet assay and γ‐H<jats:sub>2</jats:sub><jats:styled-content style="fixed-case">AX</jats:styled-content> immunostaining.</jats:p></jats:sec><jats:sec><jats:title>Result</jats:title><jats:p>We observed that recurrence could be associated with upregulated status of p‐p38 and p38α gene in cut margin area of <jats:styled-content style="fixed-case">HNSCC</jats:styled-content> patients as compared to tumor region. p38‐inhibited cells showed significantly reduced expression of <jats:styled-content style="fixed-case">CSC</jats:styled-content> markers, chemosensitivity toward cisplatin, reduced migration potential, and sphere‐forming ability along with increased apoptotic population after treatment with increasing concentration of cisplatin. p38‐inhibited cells also exhibited significantly increased comet olive tail moment and accumulation of γ‐H<jats:sub>2</jats:sub><jats:styled-content style="fixed-case">AX</jats:styled-content>, demonstrating increased <jats:styled-content style="fixed-case">DNA</jats:styled-content> damage.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This study demonstrated that p38 <jats:styled-content style="fixed-case">MAPK</jats:styled-content> activation may play a role in therapeutic resistance and disease relapse in <jats:styled-content style="fixed-case">HNSCC</jats:styled-content> by maintenance of <jats:styled-content style="fixed-case">CSC</jats:styled-content>s phenotype.</jats:p></jats:sec>