ACKR3 (Atypical Chemokine Receptor 3), also known as CXCR7. is a G protein-coupled receptor (GPCR) initially classified as a chemokine receptor due to its ability to bind chemokines CXCL12 and CXCL11. Unlike canonical chemokine receptors (e.g., CXCR4), ACKR3 lacks typical signaling pathways that drive cell migration. Instead, it functions as a scavenger or decoy receptor, regulating chemokine availability by internalizing ligands or shaping chemokine gradients. This modulation influences neighboring receptors, notably CXCR4. through ligand competition or cross-talk, impacting cell signaling in processes like embryogenesis, immune response, and tissue homeostasis.
ACKR3 is highly expressed in various cancers, including breast, lung, and glioblastoma, where it promotes tumor progression, angiogenesis, and metastasis by enhancing cell survival and invasive pathways. It also plays roles in cardiovascular development, neuroinflammation, and neuronal repair. Its dual role in health and disease has made it a compelling therapeutic target.
Antibodies targeting ACKR3 are critical tools for studying its expression, localization, and function. They enable detection in tissues (e.g., via flow cytometry, immunohistochemistry) and mechanistic studies in vitro and in vivo. Therapeutic antibodies or small-molecule inhibitors are under investigation to block ACKR3 in cancer or modulate its activity in inflammatory disorders. Challenges include ensuring specificity, avoiding off-target effects on related receptors (e.g., CXCR4), and understanding context-dependent roles in different pathologies. Ongoing research aims to clarify its complex biology and translate findings into clinical applications.