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The relationship between EMT, CD44(high)/EGFR(low) phenotype, and treatment response in head and neck cancer cell lines
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
2016 (English)In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 45, no 9, 640-646 p.Article in journal (Refereed) Published
Abstract [en]

BackgroundHead and neck squamous cell carcinoma (HNSCC) tumors are often therapy resistant and may originate from cancer stem cells or tumor cells with an epithelial-to-mesenchymal transition (EMT) phenotype. The aim of this study was to characterize HNSCC cell lines with regard to EMT profile and to investigate the influence of EMT on the response to treatment. MethodsmRNA expression of the EMT-associated genes CDH1 (E-cadherin), CDH2 (N-cadherin), FOXC2, TWIST1, VIM (vimentin), and FN1 (fibronectin) was determined using quantitative real-time PCR. Cell morphology and migration were investigated by phase-contrast microscopy and Boyden chamber assay, respectively. The cell surface expression of CD44 and epidermal growth factor receptor (EGFR) was examined by flow cytometry. The response to radiotherapy, cetuximab, and dasatinib was assessed by crystal violet staining. ResultsA total of 25 cell lines investigated differed greatly with regard to EMT phenotype. Cell lines with an EMT expression profile showed a mesenchymal morphology and a high migratory capacity. In addition, they exhibited a high cell surface expression of CD44 and a low expression of EGFR, a pattern previously associated with stemness. When the EMT inducer transforming growth factor- (TGF-) was added to non-EMT cells, changes in treatment responses were observed. Moreover, the expression of TWIST1 was found to correlate with radioresistance. ConclusionsThe data presented in this report suggest that EMT is associated with a CD44(high)/EGFR(low) phenotype and possibly negative impact on radiotherapy response in HNSCC cell lines.

Place, publisher, year, edition, pages
WILEY-BLACKWELL , 2016. Vol. 45, no 9, 640-646 p.
Keyword [en]
CD44; dasatinib; epithelial-to-mesenchymal transition; radiation; Twist1
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-132859DOI: 10.1111/jop.12423ISI: 000385713700002PubMedID: 26757432OAI: oai:DiVA.org:liu-132859DiVA: diva2:1052395
Note

Funding Agencies|Foundation of Ake Wiberg; Swedish Cancer Society [2008/552, 2010/545]; County Council of Ostergotland; Linkoping University Hospital; Foundation of Magnus Bergvall; Cancer Foundation of Ostergotland

Available from: 2016-12-06 Created: 2016-11-30 Last updated: 2016-12-06

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Johansson, Ann-CharlotteLa Fleur, LinneaRoberg, Karin
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Division of Neuro and Inflammation ScienceFaculty of Medicine and Health SciencesDepartment of Otorhinolaryngology in Linköping
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