CXCL8 is an ELR⁺ member of the CXC chemokine family. The ELR⁺ members of this chemokine family promote angiogenesis in a direct (not shown) or serial manner. (A) In a mouse model of Kaposi sarcoma, a serial mechanism of angiogenesis is the following: VEGF activation of its receptor (VEGFR) on endothelial cells leads to upregulation of the anti-apoptotic molecule BCL2. This in turn promotes the expression of endothelial cell–derived CXCL8, which functions in an autocrine and paracrine manner to promote angiogenesis (31). (B) Other serial pathways can also promote CXCL8-dependent angiogenesis, such as the signaling pathways induced by intracellular ROS, EGF, and HGF, which lead to nuclear translocation of NF-κB, expression of CXCL8 by tumor cells, and subsequent tumor-associated angiogenesis (32–35). EGFR, EGF receptor; HGFR, HGF receptor.