Chemokines are a superfamily of low molecular weight cytokines that were initially described based on their ability to induce the directed migration of leukocytes to sites of inflammation or injury. In humans, there are approximately 45 chemokines that bind to 19 G-protein-coupled receptors. In addition to mediating cellular migration, chemokines have now been shown to affect many cellular functions including survival, adhesion, invasion, proliferation, and to regulate circulating chemokine levels. Although chemokine receptors were first described on leukocytes, it is now appreciated that chemokine receptors are also expressed by many other cells including endothelial and epithelial cells.
Since the first description of chemokine receptors on malignant cells in 2001, an extensive literature has developed describing the expression and function of chemokine receptors in many malignancies. These studies support the initial hypothesis that malignant cells use chemokine receptors to migrate to distant sites of ligand expression and that expression of certain receptors is associated with a poor prognosis. It has also become apparent that malignancies of different tissues may use a diverse profile of chemokine receptors and that the same receptor may mediate metastasis to different sites in tumors of different histological origins. Receptor function may also maintain survival and expansion of the primary tumor.
Chemokine Receptors in Cancer summarizes the growing body of evidence that several chemokine receptors contribute to tumor behavior. Chemokine receptors were first identified on leukocytes and mediate directed migration of many host cells to sites of ligand expression. It is now well established that most malignant cells also express one or more chemokine receptor. This book describes our current understanding regarding how chemokine receptors contribute to tumor cell migration as well as cell survival and proliferation. The function of chemokine receptors expressed on host cells including antitumor immune effector cells as well as angiostatic and angiogeneic functions of chemokines acting on endothelial cells are described. The role of chemokine receptors that act as decoy receptors is also summarized. The therapeutic potential and challenges of targeting chemokine receptors or cognate ligands is also addressed.