A scenario is therefore proposed in which high levels of SOD3 differentially regulates the transcription of LAMA4 and LAMA5 specifically in tumor endothelium by acting on distinct transcriptional regulators: the stabilization of HIF-2α for LAMA4 induction, and the inhibition of NF-κB for LAMA5 repression (see graphical abstract). This evidence concerns the gene EPAS1 and neoplasm.