The role of the CXC chemokines platelet factor-4 (CXCL4/PF-4) and its variant (CXCL4L1/PF-4var) in inflammation, angiogenesis and cancer.
Chemokines are chemotactic cytokines which recruit leukocytes to inflammatory sites. They also affect tumor development and metastasis by acting as growth factor, by attracting pro- or anti-tumoral leukocytes or by influencing angiogenesis. Platelet factor-4 (CXCL4/PF-4) was the first chemokine shown to inhibit angiogenesis. CXCL4L1/PF-4var, recently isolated from thrombin-stimulated platelets, differing from authentic CXCL4/PF-4 in three carboxy-terminally located amino acids, was found to be more potent than CXCL4/PF-4 in inhibiting angiogenesis and tumor growth. Both glycosaminoglycans (GAG) and CXCR3 are implicated in the activities of the PF-4 variants. This report reviews the current knowledge on the role of CXCL4/PF-4 and CXCL4L1/PF-4var in physiological and pathological processes. In particular, the role of CXCL4/PF-4 in cancer, heparin-induced thrombocytopenia and atherosclerosis is described.
Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven (KULeuven), Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Jo
J
Vandercappellen
Jo
J
Van Damme
Sofie
S
Struyf
D000818:Animals; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000209:etiology* / Q000235:genetics; D008954:Models, Biological; D009369:Neoplasms / Q000098:blood supply / Q000150:complications / Q000209:etiology* / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000235:genetics / Q000628:therapy; D018919:Neovascularization, Physiologic / Q000235:genetics* / Q000502:physiology; D010978:Platelet Factor 4 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use
C064936:PF4V1 protein, human; D010978:Platelet Factor 4