Mini Review

Clinical Importance and Therapeutic Implications of the Pivotal CXCL12-CXCR4 (Chemokine Ligand-Receptor) Interaction in Cancer Cell Migration
Manit Arya, Hashim Ahmed, Nitika Silhi, Magali Williamson, Hiten R.H. Patel

University College London, London, UK; University of Rochester Medical Center, Rochester, N.Y., USA

Address of Corresponding Author

Tumor Biol 2007;28:123-131 (DOI: 10.1159/000102979)

  Key Words

• Cancer
• Chemokines
• CXCR4
• CXCL12
• Stromal cell-derived factor-1

  Abstract

Chemokines are small, secreted proteins and are now the largest known cytokine family. They mediate their effects through a family of G-protein-coupled receptors and were initially recognized for their ability to act as chemo-attractants and activators of specific types of leucocytes in a variety of immune and inflammatory responses. However, during the past 5 years there has been a chemokine revolution in cancer and all scientists and clinicians in oncology-related fields are now aware of their crucial role at all stages of neoplastic transformation and progression. The most important chemokine ligand-receptor interaction is that of the CXCL12 (stromal cell-derived factor-1, SDF-1) ligand with its exclusive receptor CXCR4; this interaction has a pivotal role in the directional migration of cancer cells during the metastatic process. This has been demonstrated by in vitro and in vivo experiments in addition to retrospective clinical studies. These findings have exciting implications in the field of cancer therapeutics, with several small molecule CXCR4 antagonists having been developed, which may provide clinical benefit in the therapy of cancer metastasis. Interestingly, it is likely that the effect of the anti-HER2 antibody [trastuzumab (Herceptin®)] in breast cancer involves downregulation of the CXCR4 receptor. Unfortunately, a major problem is that chemokine receptors are expressed in other cells within the body, particularly those of the immune system and it is not clear what effects long-term CXCR4 antagonism could have on innate and adaptive immunity. However, there is little doubt that the great strides made in elucidating the complex relationship between chemokines and their role in cancer will soon translate into significant survival benefits for patients.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Manit Arya
University College London
48 Riding House Street
London WC1E 6BT (UK)
Tel. +44 7930 548 021, Fax +44 1253 302 615, E-Mail manit_arya@hotmail.com

  Article Information

Received: September 8, 2006
Accepted after revision: December 1, 2006
Published online: May 18, 2007
Number of Print Pages : 9
Number of Figures : 2, Number of Tables : 0, Number of References : 86