Clinical relevance of chemokine receptor CXCR4

Stromal cell-derived factor-1 (SDF-1/CXCL12) induces intracellular signaling pathways crucial for mobilization, migration, proliferation and survival of many cell types via CXCR4, a chemokine CXC-motif receptor, member of the G protein-coupled receptor family. Despite playing a key role in such major processes as embryogenesis, cell differentiation and organ regeneration, molecular mechanisms underlying CXCR4 signaling remain elusive, even more so, as CXCR4 seems to activate both G-protein-dependent and G-protein-independent pathways. CXCR4 is expressed on multiple cell types including lymphocytes, hematopoietic stem cells, endothelial and epithelial cells, and cancer cells. In fact, overexpression of this receptor has been detected in many different types of cancer. The SDF-1/CXCR4 axis is also involved in tumor progression, angiogenesis, metastasis, and survival. This pathway is therefore a target for therapeutics that can block the SDF-1/CXCR4 interaction or inhibit downstream intracellular signaling. Clinical mobilization of hematopoietic stem cells (HSC), a nowadays popular method of collecting material for hematopoietic progenitor stem cell transplantation, is also dependent on the SDF-1/CXCR4 axis. Granulocyte colony-stimulating factor (G-CSF), administered to a transplant donor during clinical treatment, violates interactions between CXCR4 and its ligand, which results in degradation of HSC anchorage in bone marrow and the release of these cells into peripheral blood.In this paper we describe the clinical significance of CXCR4 and its ligand, as well as the role of CXCR4 and its gene polymorphisms in disease susceptibility.