Chemokine Receptors in Cancer (Cancer Drug Discovery and Development)

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. 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. Front Matter....Pages i-x Chemokines and Chemokine Receptors in Cancer Progression....Pages 1-30 CXCR4 and Cancer....Pages 31-45 HIF-1 Regulation of Chemokine Receptor Expression....Pages 47-61 Chemokine Receptors Involved in Colon Cancer Progression, and Lymph Node Metastasis....Pages 63-78 The CXCR3/CXCL3 Axis in Cancer....Pages 79-91 Roles for CCR7 in Cancer Biology....Pages 93-108 The CCL5/CCR5 Axis in Cancer....Pages 109-130 CXC Chemokines in Cancer Angiogenesis....Pages 131-151 The Roles of Chemokines and Chemokine Receptors in Prostate Cancer....Pages 153-170 Back Matter....Pages 171-176 Chemokines are a superfamily of low molecular weight cytokines. In humans, there are approximately 45 chemokines that bind to 19 G-protein-coupled receptors. This book reviews what we do and do not know about the role of chemokine receptors in cancer behavior.