Cxcr4-KO Mouse

Cxcr4, also known as fusin or CD184, is a 7-transmembrane helix G-protein-coupled receptor encoded by the CXCR4 gene. It plays a central role in cell migration, hematopoiesis, cell homing, and retention in the bone marrow. By binding to its ligand CXCL12 (SDF-1), it triggers multiple signaling pathways, which are crucial for various physiological processes such as the development of the immune system [1,2,4].

In cancer, overexpression of Cxcr4 in tumor tissues has a high correlation with tumor aggressiveness, metastasis, and recurrence. For example, in gastrointestinal cancer, a meta-analysis showed that high Cxcr4 expression in oesophagus, gastric, and colorectal cancer predicted a worse prognosis [5]. In glioblastoma, Cxcr4 and its ligand maintain the epithelial-mesenchymal transition, cancer stem cell generation and self-renewal, and the perivascular stem cell niche, suggesting that Cxcr4 antagonists could be used for treatment [3]. In hematological malignancies, the Cxcr4/Cxcl12 axis drives disease progression, and CXCR4 inhibitors show promise in reducing tumor burden and sensitizing malignant cells to chemotherapy [6].

In conclusion, Cxcr4 is essential for multiple physiological processes and is closely associated with various diseases, especially cancer. The study of Cxcr4, including through gene knockout or conditional knockout mouse models (although not explicitly detailed in the given references), could potentially lead to a better understanding of disease mechanisms and the development of more effective therapeutic strategies for diseases like cancer and hematological malignancies.

References:

1. Bianchi, Marco E, Mezzapelle, Rosanna. 2020. The Chemokine Receptor CXCR4 in Cell Proliferation and Tissue Regeneration. In Frontiers in immunology, 11, 2109. doi:10.3389/fimmu.2020.02109. https://pubmed.ncbi.nlm.nih.gov/32983169/

2. Yu, Jingjing, Zhou, Xu, Shen, Langtao. 2023. CXCR4-Targeted Radiopharmaceuticals for the Imaging and Therapy of Malignant Tumors. In Molecules (Basel, Switzerland), 28, . doi:10.3390/molecules28124707. https://pubmed.ncbi.nlm.nih.gov/37375261/

3. Richardson, Peter J. . CXCR4 and Glioblastoma. In Anti-cancer agents in medicinal chemistry, 16, 59-74. doi:. https://pubmed.ncbi.nlm.nih.gov/26299663/

4. Khamyath, Mélanie, Bonaud, Amélie, Balabanian, Karl, Espéli, Marion. 2023. [CXCR4 as a rheostat of humoral response]. In Medecine sciences : M/S, 39, 23-30. doi:10.1051/medsci/2022192. https://pubmed.ncbi.nlm.nih.gov/36692314/

5. Jiang, Qingtao, Sun, Yun, Liu, Xin. 2019. CXCR4 as a prognostic biomarker in gastrointestinal cancer: a meta-analysis. In Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals, 24, 510-516. doi:10.1080/1354750X.2019.1637941. https://pubmed.ncbi.nlm.nih.gov/31244335/

6. Martino, Enrica Antonia, Bruzzese, Antonella, Labanca, Caterina, Vigna, Ernesto, Gentile, Massimo. 2024. Investigational CXCR4 inhibitors in early phase development for the treatment of hematological malignancies. In Expert opinion on investigational drugs, 33, 915-924. doi:10.1080/13543784.2024.2388567. https://pubmed.ncbi.nlm.nih.gov/39096094/