Under the tight regulation of TIE2 signaling, TMEM macrophages secrete large amounts of vascular endothelial growth factor (VEGF), which in turn, functions in a paracrine fashion on the TMEM endothelial cell to promote the reversible breakdown of endothelial cell-to-cell adhesions, localized vasculature opening, and the subsequent intravasation of invasive/migratory tumor cells from the immediate area surrounding the TMEM doorway. This evidence concerns the gene VEGFA and neoplasm.