Tumor-derived EVs carrying VEGF and remodeling enzymes promote endothelial permeability. TAMs stimulate angiogenesis and guide tumor cells to blood vessels, disrupting endothelial barriers for intravasation. CXCL12/CXCR4 signaling recruits neutrophils to tumor cells, facilitating early metastatic events. This evidence concerns the gene CXCR4 and neoplasm.