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The relationship between EMT, CD44 high /EGFR low phenotype, and treatment response in head and neck cancer cell lines
Author(s) -
Johansson AnnCharlotte,
La Fleur Linnea,
Melissaridou Styliani,
Roberg Karin
Publication year - 2016
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12423
Subject(s) - cd44 , epithelial–mesenchymal transition , cancer research , head and neck squamous cell carcinoma , biology , radioresistance , cancer stem cell , cell culture , cell , vimentin , epidermal growth factor receptor , stem cell marker , cancer cell , cancer , pathology , stem cell , medicine , immunology , head and neck cancer , immunohistochemistry , microbiology and biotechnology , metastasis , genetics
Background Head 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. Methods mRNA expression of the EMT ‐associated genes CDH 1 (E‐cadherin), CDH 2 (N‐cadherin), FOXC 2 , TWIST 1 , VIM (vimentin), and FN 1 (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 CD 44 and epidermal growth factor receptor ( EGFR ) was examined by flow cytometry. The response to radiotherapy, cetuximab, and dasatinib was assessed by crystal violet staining. Results A 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 CD 44 and a low expression of EGFR , a pattern previously associated with stemness. When the EMT inducer transforming growth factor‐β ( TGF ‐β) was added to non‐ EMT cells, changes in treatment responses were observed. Moreover, the expression of TWIST 1 was found to correlate with radioresistance. Conclusions The data presented in this report suggest that EMT is associated with a CD 44 high / EGFR low phenotype and possibly negative impact on radiotherapy response in HNSCC cell lines.