Erythropoietin Stimulates Tumor Growth via EphB4
Menée in vitro, in vivo et à l'aide d'échantillons tumoraux prélevés sur des patientes atteintes d'un cancer de l'ovaire ou du sein, cette étude met en évidence des mécanismes par lesquels, suite à l'administration d'un traitement visant à lutter contre une anémie induite par la chimiothérapie, un récepteur de l'érythropoïétine, EphB4, favorise la progression d'une tumeur de l'ovaire ou du sein
While recombinant human erythropoietin (rhEpo) has been widely used to treat anemia in cancer patients, concerns about its adverse effects on patient survival have emerged. A lack of correlation between expression of the canonical EpoR and rhEpo?s effects on cancer cells prompted us to consider the existence of an alternative Epo receptor. Here, we identified EphB4 as an Epo receptor that triggers downstream signaling via STAT3 and promotes rhEpo-induced tumor growth and progression. In human ovarian and breast cancer samples, expression of EphB4 rather than the canonical EpoR correlated with decreased disease-specific survival in rhEpo-treated patients. These results identify EphB4 as a critical mediator of erythropoietin-induced tumor progression and further provide clinically significant dimension to the biology of erythropoietin.