CXCL12

What is CXCL12 protein?

CXCL12 gene (C-X-C motif chemokine ligand 12) is a protein coding gene which situated on the long arm of chromosome 10 at locus 10q11. CXCL12, also known as SDF-1, is a small protein that belongs to the CXC chemokine family. It plays a role in a variety of physiological processes, including cell chemotaxis, migration, and activation, especially in embryonic development, immune surveillance, inflammatory response, tissue homeostasis, and tumor growth and metastasis. CXCL12 functions by binding to its receptors, CXCR4, its main classical G-protein-coupled receptor, and CXCR7, which acts primarily as a scavenger of CXCL12 and also transmits signals through the β-arrestin pathway. The CXCL12 protein is consisted of 93 amino acids and CXCL12 molecular weight is approximately 10.7 kDa.

What is the function of CXCL12 protein?

CXCL12 is a potent chemoattractant for various cell types, including lymphocytes, monocytes, and stem cells, guiding their migration to specific tissues. CXCL12 is critical for the localization and development of hematopoietic stem cells within the bone marrow. It helps in the trafficking and positioning of immune cells, contributing to the immune response. CXCL12 is involved in the recruitment of immune cells to sites of inflammation. It aids in the recruitment of stem and progenitor cells to damaged tissues, promoting healing and regeneration. It plays a role in the maintenance of bone homeostasis by regulating the function of osteoblasts, osteoclasts, satellite cells, and myoblasts.

Fig1. Emerging Roles of the CXCL12 Axis in the Regulation of Epithelial-to-Mesenchymal Transition (EMT). (Dimitra P Anastasiadou, 2024)

CXCL12 related signaling pathway

CXCL12 activates a variety of signaling pathways by binding to CXCR4, such as the PI3K-AKT-NF-κB axis and signaling through MEK1/2 and Erk 1/2, promoting gene expression and cell cycle progression. Activation of these signaling pathways can lead to cell migration and survival, and even proliferation. The roles of the CXCL12/CXCR4 axis in the tumor microenvironment include promoting tumor growth, invasion, and metastasis, and maintaining tumor cell survival in some hematological malignancies. In addition, the CXCL12/CXCR4 signaling pathway is involved in hematopoietic stem cell migration and localization, as well as cell recruitment during tissue injury and repair.

CXCL12 related diseases

It plays a key role in tumor growth, angiogenesis, cell adhesion, and metastasis by binding to the CXCR4 and CXCR7 receptors. CXCL12 is particularly important in the tumor microenvironment, and its increased expression level is closely related to tumor aggressiveness and prognosis. For example, in tumors, the high expression of CXCL12 can promote the proliferation of tumor cells, enhance the adhesion ability of tumor cells, and participate in the process of tumor metastasis. In addition, the CXCL12/CXCR4 signaling pathway is involved in the angiogenesis process after ischemic stroke by promoting the proliferation and migration of vascular endothelial cells. In central nervous system diseases, CXCL12 also plays a role and is strongly associated with diseases such as amyotrophic lateral sclerosis, Alzheimer's disease and multiple sclerosis. The CXCL12/CXCR4 axis may also be involved in inflammatory responses and the mobilization of neural progenitor cells, potentially affecting the repair process after stroke.

Bioapplications of CXCL12

Studies have shown that the use of CXCR4 antagonists can block the interaction between CXCL12 and CXCR4, thereby inhibiting the proliferation, invasion and metastasis of tumor cells, and may reduce the angiogenesis and metastasis ability of tumors. In addition, blocking the CXCL12/CXCR4 axis may also enhance the immune response in the tumor microenvironment, providing a new strategy for tumor immunotherapy. In addition to tumor therapy, CXCL12 also shows potential in the treatment of other diseases, such as stroke and cardiovascular disease. In addition, CXCL12 also shows great application potential in tissue repair and regenerative medicine. For example, CXCL12 promotes the homing and differentiation of stem cells and helps repair damaged tissues. In terms of drug delivery systems, nanodrug delivery systems based on the CXCL12/CXCR4 axis are being developed to improve drug targeting and therapeutic efficacy.