CXCL12 (stromal cell-derived factor-1, SDF-1), is a small protein that belongs to the chemokine family, whose members have a crucial role in directing cell migration. It is ubiquitously expressed in many tissues and cell types. CXCL12 acts through two receptors, CXCR4 and CXCR7. While the former is a classic G protein-coupled transmembrane chemokine receptor, the latter primarily function as a scavenger of CXCL12. CXCL12 is a chemoattractant for T-lymphocytes and monocytes, but not neutrophils. CXCL12 has an essential role in neural and vascular development, hematopoiesis, cancer and in immunity[1][2][3].
CXCL12 gene in human is located on chromosome 10 (10q11.21) and recognizes seven isoforms deriving from alternative gene splicing (α, β, γ, δ, ε, θ) with α and β being the most studied and three (CXCL12α to γ) in mice. CXCL12 is described classically as a homing chemokine as it exhibits chemoattraction of tumoral cells toward the target tissues. CXCL12, although being homeostatic in classification, also takes inflammatory activities. CXCL12 binds to glycosaminoglycans (GAGs) exposed on the surface of endothelial cells through a cluster of basic residues-the BBXB motif (B for basic amino acid and X any amino acid) generating its chemotactic gradients and promoting leukocyte/cancer cell migration. CXCL12/CXCR4 axis is involved in tumor progression, angiogenesis, metastasis, and survival. CXCR7 binds with high-affinity CXCL12 and with lower-affinity CXCL11. Although CXCR7 acts as a CXCL12 scavenger through ligand internalization and degradation, it transduces the signal mainly through β-arrestin with a pivotal role in endothelial and neural cells. CXCL12 is constitutively expressed in several organs including lung, liver, skeletal muscle, brain, kidney, heart, skin, and bone marrow. CXCL12 secretion is also associated with tissue damage such as heart infarct, limb ischemia, toxic liver damage, excessive bleeding, total body irradiation, and after tissue damage related to chemotherapy. CXCR4 is expressed by endothelial cells and pericytes of hypoxic, injured, or pathological tissues, including injured carotid arteries and atherosclerotic plaques[1][2].
