Involvement of chemokine receptors in organ-specific metastasis.

The chemokines are a family of small proteins known for their ability to control cell migration in the body. Their receptors belong to the class A subfamily of G protein-coupled receptors. In recent years, chemokines have grown in importance, because they are involved in inflammation and autoimmune disease. Some of them are also involved in infectious disease, since two chemokine receptors, CXCR4 and CCR5, are used by the human immunodeficiency virus (HIV) to gain entry to cells. Several years ago it also became clear that chemokines can also influence tumor cells. Specifically, tumor cells express chemokine receptors in a nonrandom manner, and this suggested a role for chemokines in the metastatic destination of tumor cells. By far the most common chemokine receptor expressed by many cancer cells is CXCR4. Its ligand, CXCL12, is strongly expressed in lung, liver, bone marrow and lymph nodes, places that represent common metastatic destinations in many cancers. Many studies have now validated the concept that chemokines and their receptors influence metastasis. The potential therapeutic importance of these observations depends on the role that each metastatic destination such as liver, lung, bone marrow, etc., plays in the prognosis of a cancer patient.