CXCL12 and neoplasm: In established tumors, macrophages stimulate tumor growth, migration, angiogenesis, and metastasis via the following mechanisms: (1) Macrophages create and maintain the tumor vascular network by producing and releasing pro-angiogenic cytokines, such as vascular endothelial growth factor-α (VEGF-α) and angiogenic CXC chemokines (CXCL8 and CXCL12), transforming growth factor-β (TGF-β) and TNF-α (Noy and Pollard, 2014; Cassetta and Pollard, 2018).