The role of chemokines in melanoma tumor growth and metastasis.

Chemokines represent a large family of polypeptide signaling molecules that are notable for their role in chemotaxis, leukocyte homing, directional migration, and G protein coupled receptor activation. Chemo kines have recently been implicated in tumor progression and metastasis. The demonstration of chemokine expression and receptor activation in melanoma tumor cells themselves, and the tumor infiltrating leukocytes, may have important implications in terms of tumor progression and tumor cell homing to metastatic sites. In addition to their chemotactic and cell homing properties, chemokines and their receptors also play a part in other biologic functions relevant to oncogenesis, including cell proliferation, protease induction, tumor growth, and angiogenesis. Melanomas, and the cells derived from them, have been found to express a number of chemokines, including CXCL8 (interleukin-8), CXCL1-3 (MGSA-GROalpha-gamma), CCL5 (RANTES), and CCL2 (monocyte chemotactic protein-1), which have been implicated in tumor growth and progression. Furthermore, recent studies have demonstrated organ-specific patterns of melanoma metastasis that correlate with their expression of specific chemokine receptors, including CXCR4, CCR7, and CCR10. This review will focus on the current biology of chemokines and chemokine receptors in the context of understanding their potential roles in melanoma progression and metastasis, and is not meant to be a comprehensive review of chemokine biology. Continued understanding and progress in the determination of the role of chemokines and their receptors in tumorigenesis and metastasis, including melanoma, may lead to novel approaches in the treatment and management of this disease.