Role of the CXCR4/CXCL12 signaling axis in breast cancer metastasis to the brain.
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.
Hinton
Cimona V
CV
Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, 4 Blackfan Circle, 3rd Floor, Boston, MA 02115, USA.
Avraham
Shalom
S
Avraham
Hava Karsenty
HK
D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D054377:Chemokine CXCL12 / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D036341:Intercellular Signaling Peptides and Proteins; D019718:Receptors, CXCR4