title: Epidermal growth factor-induced modulation of cytokeratin expression levels influences the morphological phenotype of head and neck squamous cell carcinoma cells.
abstract: The migratory ability of tumor cells requires cytoskeletal rearrangement processes. Epidermal growth factor receptor (EGFR)-signaling tightly correlates with tumor progression in head and neck squamous cell carcinomas (HNSCCs), and has previously been implicated in the regulation of cytokeratin (CK) expression. In this study, HNSCC cell lines were treated with EGF, and CK expression levels were monitored by Western blot analysis. Changes in cellular morphology were documented by fluorescence- and atomic force microscopy. Some of the cell lines demonstrated an EGF-dependent modulation of CK expression levels. Interestingly, regression of some CK subtypes or initial up-regulation followed by downregulation at higher EGF-levels could also be observed in the tested cell lines. Overall, the influence of EGF on CK expression levels appeared variable and cell-type-dependent. Real-time cellular analysis of EGF-treated and -untreated HNSCC cell lines demonstrated a rise over time in cellular impedance. In three of the EGF-treated HNSCC cell lines, this rise was markedly higher than in untreated controls, whereas in one of the cell lines the gain of cellular impedance was paradoxically reduced after EGF treatment, which was found to correlate with changes in cellular morphology rather than with relevant changes in cellular viability or proliferation. After treating HNSCC cells with EGF, CK filaments frequently appeared diffusely distributed throughout the cytoplasm, and in some cases were found in a perinuclear localization, the latter being reminiscent to observations by other groups. In summary, the data points to a possible role of EGFR in modulating HNSCC cell morphology.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Giessen and Marburg, Baldingerstrasse, Marburg, Germany.
authors.forename: Galina
authors.initials: G
authors.lastname: Makarova
authors.forename: Michael
authors.initials: M
authors.lastname: Bette
authors.forename: Ansgar
authors.initials: A
authors.lastname: Schmidt
authors.forename: Ralf
authors.initials: R
authors.lastname: Jacob
authors.forename: Chengzhong
authors.initials: C
authors.lastname: Cai
authors.forename: Fiona
authors.initials: F
authors.lastname: Rodepeter
authors.forename: Thomas
authors.initials: T
authors.lastname: Betz
authors.forename: Johannes
authors.initials: J
authors.lastname: Sitterberg
authors.forename: Udo
authors.initials: U
authors.lastname: Bakowsky
authors.forename: Roland
authors.initials: R
authors.lastname: Moll
authors.forename: Andreas
authors.initials: A
authors.lastname: Neff
authors.forename: Andreas
authors.initials: A
authors.lastname: Sesterhenn
authors.forename: Afshin
authors.initials: A
authors.lastname: Teymoortash
authors.forename: Matthias
authors.initials: M
authors.lastname: Ocker
authors.forename: Jochen A
authors.initials: JA
authors.lastname: Werner
authors.forename: Robert
authors.initials: R
authors.lastname: Mandic
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D007633:Keratins / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D010641:Phenotype; D051191:Plakophilins / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D051191:Plakophilins; D004815:Epidermal Growth Factor; D007633:Keratins