CXCR4 Specific Neutra™ Antibody Products
Product listC-X-C Motif Chemokine Receptor 4 (CXCR4), also known as Cluster of Differentiation 184 (CD184) and Fusin, is a 352 aa CXCR4 gene encoding G-protein-coupled receptor (GPCR), which is initially identified as a chemokine receptor involved with breast cancer metastasis to the lung tissues. CXCR4 is an integral membrane protein expressed among more than 23 cancers, including breast cancer, ovarian cancer, melanoma, prostate cancer, and CRC, while its expression in many normal tissues is absent or low. In the plasma membrane, CXCR4 can exist in the form of monomers, dimers, nanoclusters, or oligomers.
Its Gene ID: 7852, UniProtKB ID: P61073, and OMIM ID: 162643.
Fig.1 Structure of CXCR4.Distributed under CC BY-SA 3.0, from Wiki, without modification.
CXCR4 Functions and Signaling Pathways
CXCR4 triggers not only multiple G protein-dependent signaling pathways, including AKT, mTOR, PI3K, and EGFR signaling pathways, but also G protein-independent signaling pathways, including JAK/STAT, ERK, and p53 MAPK pathways. In normal tissues, CXCR4 signaling participates in the regulation of a variety of events, such as tissue repair, embryogenesis, hematopoiesis, immune response, and organogenesis. In cancers, CXCR4 expression is reported to be involved with critical consequences on tumor progression, especially the proliferation, differentiation, metastasis, invasion, and angiogenesis of cancer cells.
The most well-investigated ligand of CXCR4 is CXCL12, also recognized as stromal cell-derived factor-1 (SDF-1), binding and activating CXCR4, thus triggering downstream signaling pathways. In cancer progression, the expression of receptor CXCR4 is stimulated by acetylation or hypomethylation which arouses its recruitment on membranes. CXCL12 binds to CXCR4 and activates the downstream signaling, enhancing events like proliferation, angiogenesis, and invasion.
In addition, cells with CXCR4 expression can be attracted by distant organs with increased CSCL12 release, leading to the homing of cancer cells. Therefore, significantly increased CXCR4/CXCL12 expression levels can be regarded as promising biomarkers for diagnostic or prognostic purposes.
Fig.2 CXCR4 in cancer progression1
CXCR4 as A Therapeutic Target
Considering that the CXCL12-CXCR4 axis is closely associated with tumor growth, survival, angiogenesis, metastasis, as well as drug resistance, targeting CXCR4 has emerged as a promising strategy for cancer research and therapeutic intervention. There are numerous modulators of the CXCL12-CXCR4 axis, including monoclonal antibodies (mAb) targeting CXCR4, which are in different stages of preclinical or clinical studies against a wide range of cancers. For example, it is demonstrated that in multiple myeloma (MM), an anti-CXCR4 antibody that is fully humanized, significantly suppresses the MM cell proliferation and tumor growth in vitro and inhibits MM xenografts in mouse models. Its therapeutic effects have also been proved when applied for therapy in acute myeloid leukemia, non-Hodgkin lymphoma, and chronic lymphocytic leukemia.
Creative Biolabs offers different anti-CXCR4 antibody products. These antibodies are recombinantly expressed and could be used for various purposes. Customization of CXCR4-based neutralizing antibodies is also available for you here.
REFERENCE
- Alsayed, Reem Khaled ME, et al. "Epigenetic regulation of CXCR4 signaling in cancer pathogenesis and progression." Seminars in Cancer Biology. Vol. 86. Academic Press, 2022. Under open access license CC BY 4.0, without modification.
