CXCR4 and cancer: Hypoxia-induced CXCL12 and ANGPT2 expression stimulated the recruitment and revascularization of perivascular aggregates of TAMs expressing CXCR4 and TIE2, respectively. The ANGPT2-TIE2 signaling pathway promotes pro-angiogenic interactions between perivascular TAMs and neoplastic tumor-associated vessels, while the TIE2 + perivascular TAMs-induced VEGF-A signaling pathway leads to a vascular transient increase in permeability that promotes endocytosis by cancer cells [37, 55].