Platelet factor-4 (CXCL4/PF-4): An angiostatic chemokine for cancer therapy

Platelet factor-4 (CXCL4/PF-4) is the first chemokine identified to have several biological functions. Notably, CXCL4/PF-4 inhibits endothelial cell proliferation and migration, leading to suppression of angiogenesis. Since angiogenesis is essential for the growth of most primary tumors and their subsequent metastases, it is a target for cancer therapy; due to its multiple functions, CXCL4/PF-4 is a potential clinical anti-tumor agent. This report reviews the mechanisms of CXCL4/PF-4 angiostatic activity, including interference with angiogenic growth factors bFGF-2 and VEGF165, activation of CXCR3B, interactions with integrins, interference with cell cycle, interactions with factors such as VEGF121 and CXCL8/IL-8, and derived molecules of CXCL4/PF-4 with angiostatic and anti-tumoral activities in different models in vivo or in vitro.

► CXCL4/PF-4 has several biological functions, including angiogenesis inhibition. ► Five potential mechanisms are invoked to induce CXCL4/PF-4 angiostatic activity. ► CXCL4/PF-4, and numerous derived molecules of CXCL4/PF-4 have the angiostatic effect.