Chemokines are peptide ligands known for their ability to direct the movement of cells of the immune system. Müller et al. show that breast cancer cells express amounts of the chemokine receptors, CXCR4 and CCR7, greater than those in normal breast epithelial tissue. Furthermore, the stimulation of migratory behavior of breast cancer cells by purified chemokines (CXCL12 and CCL21) or by protein extracts from tissues that are preferred breast cancer secondary sites was inhibited by neutralizing antibodies against the receptor CXCR4 or the chemokine CXCL12. In a mouse model of metastatic breast cancer, treatment of the animals with antibodies against CXCR4 decreased metastasis to the lung and the lymph nodes, two tissues with high levels of CXCL12. These data suggest that the choice of metastatic sites for breast cancer cells is mediated in part by a chemokine pathway through the interaction of tissue-derived CXCL12 and tumor-expressed CXCR4 (see the accompanying article by Liotta).
A. Müller, B. Homey, H. Soto, N. Ge, D. Catron, M. E. Buchanan, T. McClanahan, E. Murphy, W. Yuan, S. N. Wagner, J. L. Barrera, A. Mohar, E. Verástegui, A. Zlotnik, Involvement of chemokine receptors in breast cancer metastasis. Nature 410, 50-56 (2001). [Online Journal]
L. A. Liotta, An attractive force in metastasis. Nature 410, 24-25 (2001). [Online Journal]