The role of the CXC chemokines platelet factor-4 (CXCL4/PF-4) and its variant (CXCL4L1/PF-4var) in inflammation, angiogenesis and cancer

Cytokine Growth Factor Rev. 2011 Feb;22(1):1-18. doi: 10.1016/j.cytogfr.2010.10.011. Epub 2010 Nov 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Inflammation / complications
  • Inflammation / etiology*
  • Inflammation / genetics
  • Models, Biological
  • Neoplasms / blood supply
  • Neoplasms / complications
  • Neoplasms / etiology*
  • Neoplasms / therapy
  • Neovascularization, Pathologic / etiology*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / therapy
  • Neovascularization, Physiologic / genetics*
  • Neovascularization, Physiologic / physiology
  • Platelet Factor 4 / genetics
  • Platelet Factor 4 / pharmacology
  • Platelet Factor 4 / physiology*
  • Platelet Factor 4 / therapeutic use


  • PF4V1 protein, human
  • Platelet Factor 4