CXCL12 (SDF-1)/CXCR4 Pathway in Cancer

Chemokines, small proinflammatory chemoattractant cytokines that bind to specific G-protein-coupled seven-span transmembrane receptors, are major regulators of cell trafficking and adhesion. The chemokine CXCL12 stromal cell-derived factor-1 (SDF-1) binds primarily to CXC receptor 4 (CXCR4; CD184). The binding of CXCL12 to CXCR4 induces intracellular signaling through several divergent pathways initiating signals related to chemotaxis, cell survival and/or proliferation, increase in intracellular calcium, and gene transcription. CXCR4 is expressed on multiple cell types including lymphocytes, hematopoietic stem cells, endothelial and epithelial cells, and cancer cells. The CXCL12/CXCR4 axis is involved in tumor progression, angiogenesis, metastasis, and survival. This pathway is a target for therapeutics that can block the CXCL12/CXCR4 interaction or inhibit downstream intracellular signaling.