Clinical & Experimental Metastasis

, Volume 27, Issue 2, pp 97–105 | Cite as

Role of the CXCR4/CXCL12 signaling axis in breast cancer metastasis to the brain

  • Cimona V. Hinton
  • Shalom Avraham
  • Hava Karsenty Avraham


Breast cancer is the most common malignancy and second leading cause of cancer death in women. Ninety percent of mortality in breast cancer is often associated with metastatic progression or relapse in patients. Critical stages in the development of aggressive breast cancer include the growth of primary tumors and their ability to spread to foreign organs and form metastases, as well as the establishment of an independent blood supply within the new tumors. Hence, it is imperative to characterize the key molecules that regulate the metastasis of human breast cancer cells. The expression of CXCR4/CXCL12 in breast tumors has been correlated with a poor prognosis, increased metastasis, resistance to conventional therapeutic agents and a poor outcome in the pathogenesis of breast cancer. However, effective anti-CXCR4 therapy remains a challenge. Here, we will review the putative involvement of the CXCR4/CXCL12 signaling axis in breast cancer metastasis to the brain. Characterization of signaling events important for breast cancer cell growth and their metastasis to the brain should provide insights into breast cancer therapies and improved, successful treatments for breast cancer.


AKT AMD3100 Breast cancer CNS CXCL12 CXCR4 Endothelial cells HER2 Metastasis PI-3K VEGF 



Protein kinase B


Blood brain barrier


Calcium ion


Csk homologous kinase


Central nervous system


Cyclooxygenase-2 (PTGS2)


Chemokine (C-X-C motif) ligand 12


CXC chemokine receptor 4


Experimental autoimmune encephalomyelitis


Epidermal growth factor receptor


Epidermal growth factor receptor 2


Extracellular signal-regulated kinases 1 and 2


Focal adhesion kinase


Forkhead transcription factor like 1


Human brain microvascular endothelial cells


Epidermal growth factor receptor 2




Kinase insert domain receptor


Mitogen-activated protein (MAP) kinases


Matrix metalloproteinases


Nuclear factor-kappa B


Nerve growth factor




Phosphoinositide 3-kinase


Phosphoinositide phospholipase C


RNA interference


Stromal cell-derived factor-1


Transforming growth factor beta


Vascular endothelial growth factor


Vascular endothelial growth factor receptor 1


Yin Yang 1b transcription factor



Limitations of space preclude extensive citation of the literature; we apologize to those whose work is not mentioned herein. Research in this lab is supported, in part, by National Institutes of Health Grants HL80699 (SA), CA096805 (HA), HL00791708 (CVH), Army Breast Cancer Concept Award (SA), the Susan G. Komen Fellowship (SA).


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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Cimona V. Hinton
    • 1
    • 2
  • Shalom Avraham
    • 1
    • 2
  • Hava Karsenty Avraham
    • 1
    • 2
  1. 1.Division of Experimental Medicine, Beth Israel Deaconess Medical CenterHarvard Institutes of MedicineBostonUSA
  2. 2.Harvard Medical SchoolBostonUSA

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