This observation may be further explained by studies reporting that GM-CSF signals through HIF-2α to re-educate human and murine macrophages to become more M1-like while also stimulating their release of the anti-angiogenic molecule sVEGFR-1, an alternatively spliced isoform of membrane-bound VEGFR-1 to sequester excessive tumor VEGF leading to vessel regulation. This evidence concerns the gene EPAS1 and neoplasm.