Chemokine-chemokine receptor pathway as a tumor therapeutic target: the significance of SDF-1CXCR4 pair

Chemokines, a large family of chemotactic cytokines, are the major regulators of immune cell trafficking. The chemokine stromal cell-derived factor-1 (SDF-1, or CXCL12) and its cognate receptor, CXCR4 (CD184), are an important ligand-receptor pair, which play a crucial role in numerous biological processes including hematopoiesis, inflammation, angiogenesis, and cell proliferation. Moreover, accumulating evidence indicates that SDF-1-CXCR4 pair plays important roles in regulating processes essential for tumor biology. Molecular strategies aimed at inhibiting the SDF-1-CXCR4 pathway, such as small peptide CXCR4-specific antagonists, anti-CXCR4 antibodies, and small interfering RNA might therefore prevent tumor progression and metastasis. In the present Dance Round, we focus on (i) the role of the SDF-1-CXCR4 signaling in the regulation of tumor spread, growth, and vascularization, and (ii) the significance of this ligand-receptor pair as a novel therapeutic target for neoplastic disease. Biomedical Reviews 2005; 16: 77-81.