The emerging role of chemokine receptor CXCR2 in cancer progression

Chemokines and their receptors form a complex network controlling leukocyte migration, particularly during infection and inflammation. Besides their critical contributions to the immune system, they are being increasingly implicated in tumour development and metastasis. Chemokines also mediate other tumour-related processes, including angiogenesis and even chemoresistance. There are four subgroups of chemokines based on the position of the first two N-terminal cysteine residues: CXC, CC, CX3C and C. The CXC subgroup is further divided into ELR+ and ELR− chemokines. Chemokines with the ELR motif have angiogenic properties and bind mainly to CXC chemokine receptor 2 (CXCR2). CXCR2 and its ligands are intimately involved in tumour regulation and growth, and its functional inhibition shows promising results in several cancer types. This review discusses the contribution of CXCR2 to the progression of the most frequently occurring cancers including lung, prostate, breast and colorectal cancer, in addition to recent relevant data on ovarian and pancreatic cancer. Pharmacological intervention against CXCR2 and its potential therapeutic benefits are also addressed.