Focus on the role of the CXCL12/CXCR4 chemokine axis in head and neck squamous cell carcinoma

Head Neck. 2013 Dec;35(12):1819-28. doi: 10.1002/hed.23217. Epub 2013 Mar 6.


The human chemokine system includes approximately 48 chemokines and 19 chemokine receptors. The CXCL12/CXCR4 system is one of the most frequently studied that is also found overexpressed in a large variety of tumors. The CXCL12/CXCR4 axis has been increasingly identified as an important target in cancer growth, metastasis, relapse, and resistance to therapy. In this review, we highlight current knowledge of the molecular mechanisms involving chemokines CXCL12/CXCR4 and their consequences in head and neck squamous cell carcinoma (HNSCC). Overexpression of CXCL12/CXCR4 in HNSCC appears to activate cellular functions, including motility, invasion, and metastatic processes. Current findings suggest that CXCR4 and epithelial-mesenchymal transition markers are associated with tumor aggressiveness and a poor prognosis, and may be suitable biomarkers for head and neck tumors with high metastatic potential. Furthermore, knowledge of the role of CXCR4 in HNSCC could influence the development of new targeted therapies for treatment, aimed at improving the prognosis of this disease.

Keywords: SDF-1; epithelial-to-mesenchymal transition; head and neck cancer; hypoxia; invasion; metastasis.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Carcinogenesis / metabolism
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Adhesion
  • Cell Movement
  • Chemokine CXCL12 / metabolism*
  • Drug Evaluation, Preclinical
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis / prevention & control
  • Neovascularization, Pathologic / metabolism
  • Prognosis
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / metabolism*


  • Antineoplastic Agents
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Receptors, CXCR4