title: Irradiation affects cellular properties and Eph receptor expression in human melanoma cells.
abstract: X-ray irradiation influences metastatic properties of tumor cells and, moreover, metastasis and cellular motility can be modified by members of the Eph receptor/ephrin family of receptor tyrosine kinases. We hypothesized that irradiation-induced changes in cellular properties relevant for metastasis in melanoma cells could be mediated by Eph receptor/ephrin signaling. In this pilot study, we analyzed one pre-metastatic (Mel-Juso) and three metastatic human melanoma (Mel-Juso-L3, A375, and A2058) cells lines and predominantly found anti-metastatic effects of X-ray irradiation with impaired cell growth, clonal growth and motility. Additionally, we observed an irradiation-induced increase in adhesion paralleled by a decrease in migration in Mel-Juso and Mel-Juso-L3 cells and, in part, also in A375 cells. We further demonstrate a decrease of EphA2 both in expression and activity at 7 d after irradiation paralleled by an upregulation of EphA3. Analyzing downstream signaling after irradiation, we detected decreased Src kinase phosphorylation, but unchanged focal adhesion kinase (FAK) phosphorylation, indicating, in part, irradiation-induced downregulation of signaling via the EphA2-Src-FAK axis in melanoma cells. However, to which extent this finding contributes to the modification of metastasis-relevant cellular properties remains to be elucidated.
authors.affiliation: Department of Radiopharmaceutical Biology, Institute of Radiopharmacy, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany. b.mosch@hzdr.de
authors.forename: Birgit
authors.initials: B
authors.lastname: Mosch
authors.forename: Doreen
authors.initials: D
authors.lastname: Pietzsch
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
mesh_terms: D015153:Blotting, Western; D002448:Cell Adhesion / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D036342:Ephrins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D047468:Immunoprecipitation; D008545:Melanoma / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics / Q000528:radiation effects; D036082:Receptor, EphA1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014965:X-Rays
chemical_list: D036342:Ephrins; D036082:Receptor, EphA1