However, under such cultural conditions (hypoxic, serum-containing and growth-factor rich), the neutralization of secreted IGF-II was able to significantly downregulate EphB4 as well as VEGF-A suggesting a major role for IGF-II as a mediator of HIF effects in malignant mesothelioma cells. This evidence concerns the gene EPHB4 and malignant mesothelioma.