The role of chemokines in the biology and therapy of breast cancer.

Breast cancers, like other malignancies, commonly express a repertoire of both chemokines and chemokine receptors. While some are more often expressed in certain histological types, a few general concepts are emerging that provide clues to the pathobiological role of these ligand receptor pairs. The receptor CXCR4 is often expressed in solid tumors and evidence is growing that this receptor plays a role in the growth and lymph node metastasis of breast and other cancers responding to ligand expressed at metastatic sites. Likewise, CCR7 is expressed in breast and other cancers and, in some cases, is associated with more aggressive disease. Like chemokine receptors, some ligands also modulate tumor behavior. CCL5 expression is associated with more aggressive breast cancers. CXC chemokines containing the ELR motif are expressed endogenously by some cancers, act as autocrine growth factors and support tumor angiogenesis. ELR-negative CXC chemokines inhibit tumor growth and metastasis when expressed at high levels by attracting immune effector cells and inhibiting angiogenesis. The roles of other chemokine receptors and ligands are under active investigation.