Cancers that have spread from their original site—that is, metastasized—are difficult to treat and can be fatal. However, what triggers metastasis, and why secondary tumors arise in some tissues/organs but not others, has long puzzled researchers. Now, Anja Muller and colleagues at Schering-Plough's DNAX Research Institute (Palo Alto, CA) suggest that chemokines could be the fatal cue for metastasis of breast and skin cancers (Nature 410, 50–56, 2001). The researchers found that the chemokine receptor subtypes CXCR4 and CCR7 were upregulated in several lines of breast cancer cells. Furthermore, the ligands for these receptors—CXCL12 and CCL21, respectively—were present at high concentrations in organs where metastasis commonly occurs (e.g., liver, lymph, and bone). In vitro, the chemokines encouraged cultured breast cancer cells to adopt the invasive characteristics of a metastasizing cancer. Furthermore, when immune-deficient mice were treated with anti-CXCR4 or anti-CCR7 antibodies in vivo, injected human breast cancer cells were prevented from metastasizing to the lungs. Lead author Albert Zlotnik says that it is too early to predict the potential therapeutic value of chemokine inhibitors, although the mouse studies were “promising”. “One of the most pressing questions is to investigate how this model applies to other cancers,” he says. Skin cancers, for example, express an additional receptor, CCR10.