CXCL12/CXCR4 signal transduction in diseases and its molecular approaches in targeted-therapy.

Chemokines are small molecules called "chemotactic cytokines" and regulate many processes like leukocyte trafficking, homing of immune cells, maturation, cytoskeletal rearrangement, physiology, migration during development, and host immune responses. These proteins bind to their corresponding 7-membrane G-protein-coupled receptors. Chemokines and their receptors are anti-inflammatory factors in autoimmune conditions, so consider as potential targets for neutralization in such diseases. They also express by cancer cells and function as angiogenic factors, and/or survival/growth factors that enhance tumor angiogenesis and development. Among chemokines, the CXCL12/CXCR4 axis has significantly been studied in numerous cancers and autoimmune diseases. CXCL12 is a homeostatic chemokine, which is acts as an anti-inflammatory chemokine during autoimmune inflammatory responses. In cancer cells, CXCL12 acts as an angiogenic, proliferative agent and regulates tumor cell apoptosis as well. CXCR4 has a role in leukocyte chemotaxis in inflammatory situations in numerous autoimmune diseases, as well as the high levels of CXCR4, observed in different types of human cancers. These findings suggest CXCL12/CXCR4 as a potential therapeutic target for therapy of autoimmune diseases and open a new approach to targeted-therapy of cancers by neutralizing CXCL12 and CXCR4. In this paper, we reviewed the current understanding of the role of the CXCL12/CXCR4 axis in disease pathology and cancer biology, and discuss its therapeutic implications in cancer and diseases.