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.

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adhesion kinase fak epha3 metastasisrelevant cellular properties metastasis epha2srcfak axis eph receptorephrin family of receptor tyrosine kinases cell growth clonal growth epha2 src kinase phosphorylation

Birgit, Mosch Doreen, Pietzsch Jens, Pietzsch,.Irradiation affects cellular properties and Eph receptor expression in human melanoma cells.. 6 (2),113-25.

Birgit, Mosch Doreen, Pietzsch Jens, Pietzsch,"Irradiation affects cellular properties and Eph receptor expression in human melanoma cells." 6

Birgit, Mosch Doreen, Pietzsch Jens, Pietzsch,"Irradiation affects cellular properties and Eph receptor expression in human melanoma cells."