These in vivo findings help to uncover a mechanism for TMEM doorway-associated vascular opening (TAVO) where tumor cell secreted CSF-1 induces VEGF-A secretion from macrophages, leading to increased TMEM doorway activity, decreased vascular integrity at active TMEM doorways, and increased metastatic dissemination of tumor cells through TMEM doorways as CTCs. This evidence concerns the gene VEGFA and neoplasm.