Second, CXC-chemokine receptor 4 (CXCR4) signaling is potentially critical during VCO (Figure 5), as this pathway is involved in perivascular invasion of brain-metastasizing cancer cells through stimulation by brain EC-derived CXC-chemokine ligand 12 (CXCL12) (25, 74). The gene discussed is CXCR4; the disease is cancer.