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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
Review

Abstract

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.

Keywords

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

Abbreviations

Akt

Protein kinase B

BBB

Blood brain barrier

Ca2+

Calcium ion

CHK

Csk homologous kinase

CNS

Central nervous system

Cox2

Cyclooxygenase-2 (PTGS2)

CXCL12

Chemokine (C-X-C motif) ligand 12

CXCR4

CXC chemokine receptor 4

EAE

Experimental autoimmune encephalomyelitis

EGFR

Epidermal growth factor receptor

ErbB2

Epidermal growth factor receptor 2

ERK1/2

Extracellular signal-regulated kinases 1 and 2

FAK

Focal adhesion kinase

FKHRL1

Forkhead transcription factor like 1

HBMEC

Human brain microvascular endothelial cells

HER2/Neu

Epidermal growth factor receptor 2

IL

Interleukins

KDR/Flt-1

Kinase insert domain receptor

MAPK

Mitogen-activated protein (MAP) kinases

MMP

Matrix metalloproteinases

NF-κB

Nuclear factor-kappa B

NGF

Nerve growth factor

NP-1

Neuropilin-1

PI-3K

Phosphoinositide 3-kinase

PLC

Phosphoinositide phospholipase C

RNAi

RNA interference

SDF-1

Stromal cell-derived factor-1

TGF-β

Transforming growth factor beta

VEGF

Vascular endothelial growth factor

VEGFR1

Vascular endothelial growth factor receptor 1

YY1B

Yin Yang 1b transcription factor

Notes

Acknowledgements

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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