Influence of external radiation on cellular properties and Eph receptor/ephrin expression in human melanoma cells


Influence of external radiation on cellular properties and Eph receptor/ephrin expression in human melanoma cells

Mosch, B.; Pietzsch, D.; Pietzsch, J.

There is first experimental evidence that progression and metastasis of melanoma is associated with receptor tyrosine kinases (RTK) of the Eph receptor family. However, RTK can be regulated by different factors, but the influence of radiation on Eph receptors and their ligands and, furthermore, on melanoma metastasis is unclear. In this study, we radiated one pre-metastatic and three metastatic human melanoma cells lines, including one self-generated metastatic cell line with X-rays (5 and 10 Gy vs. sham). At day 1 and day 7 post radiation we analyzed cellular viability, proliferation, colony formation, migration, adhesion, and motility. Additionally, selected Eph receptors and ephrin ligands were analyzed regarding radiation-dependent changes in mRNA and protein.
In all cell lines a dose dependent decrease in viability and cell growth for up to 1 week after radiation was demonstrated. Colony formation was unaffected in pre-metastatic and only marginally influenced in metastatic cell lines. Migration and adhesion increased 1 day after radiation, while motility of all cells decreased. In contrast, 7 days after radiation, migration decreased while adhesion remained increased in treated cells. Furthermore, an increase in motility was observed in pre-metastatic cells. For EphA2 we detected an increase in mRNA in 2 of 3 metastatic cell lines, with simultaneously decreased protein level. EphA3 was found to be up-regulated in mRNA and protein in 3 of 4 cell lines. Expression of ephrinA1 and A5 was generally low and seemed unaffected by radiation, with the exception of an increase in ephrinA1 mRNA in 3 of 4 cell lines.
In conclusion, we showed that X-ray radiation strongly decreased viability and proliferation of human melanoma cells. Concerning metastatic properties, it remained ambiguous if X-ray acts pro- or anti-metastatic to melanoma cells, probably depending on cell line and time after radiation. Regarding the present data an involvement of A-type Eph receptors in radiation-mediated effects in melanoma can be hypothesized. Ongoing studies will clarify whether and how over-expression and inhibition of Eph influences metastatic properties of human melanoma cells.

  • Poster
    Keystone Symposium “Stem cells, Cancer and Metastasis”, 06.-11.03.2011, Keystone, Colorado, USA

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Publ.-Id: 16606