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The CXCL family is a significant branch of the chemokine superfamily, a group of small, secreted proteins that play a crucial role in stimulating cell migration, particularly that of white blood cells. Chemokines exert their effects by interacting with G protein-coupled receptors on the surface of cells.
Members of the CXCL family are involved in a wide range of biological processes, including tumor growth, wound healing, immune system homeostasis, and embryonic development. Due to their extensive involvement in these vital processes, the CXCL family has become a focal point in the study of complex diseases. Abnormal expression of CXCL family members often indicates disruptions in the biological processes they are involved in and may reflect the progression of related diseases such as cancer, inflammatory disorders, and metabolic conditions.
Chemokines are categorized into four groups based on the conserved cysteine motifs near their N-terminus: CCL, CXCL, XCL, and CX3CL families, with the CXCL family being one of the major chemokine families. Members of the CXCL family are predominantly secreted by tumor cells, leukocytes, fibroblasts, endothelial cells, and epithelial cells. The expression of CXCL family members significantly impacts diseases associated with chemokine dysregulation.
The structural hallmark of the CXCL family is the presence of a C-X-C motif, which consists of four highly conserved cysteines with a variable amino acid between two of them. This feature is characteristic of CXC chemokines. Further classification of CXC chemokines into ELR+ or ELR- groups, based on the presence of the ELR (glutamic acid-leucine-arginine) motif at the N-terminus, distinguishes them as either angiogenic activators or inhibitors.
ELR+ CXC chemokines include CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, CXCL8, and CXCL17, while ELR- CXC chemokines include CXCL4, CXCL9, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, and CXCL16.
Creative Biogene offers a comprehensive range of CXCL-related research products and services, including efficient gene editing tools, cell line construction, and virus packaging services, supporting researchers in exploring the potential applications of the CXCL family in cancer, immune diseases, and other fields.
| Cat.No. | Product Name | Price |
| MiUTR1M-03478 | CXCL13 miRNA 3'UTR clone | Inquiry |
| CLOE-1736 | Human CXCL8 HEK293 Cell Lysate | Inquiry |
| PMRN-0289 | Human CXCL12 mRNA | Inquiry |
| CDFG012796 | Human CXCL17 cDNA Clone(NM_198477.1) | Inquiry |
| CSC-DC003869 | Panoply™ Human CXCL2 Knockdown Stable Cell Line | Inquiry |
| CSC-SC003866 | Panoply™ Human CXCL14 Over-expressing Stable Cell Line | Inquiry |
| CSC-SC003871 | Panoply™ Human CXCL5 Over-expressing Stable Cell Line | Inquiry |
| LV10095L | human CXCL9 (NM_002416) lentivirus particles | Inquiry |
| MiUTR1M-03479 | CXCL14 miRNA 3'UTR clone | Inquiry |
| MiUTR1R-03327 | CXCL13 miRNA 3'UTR clone | Inquiry |
| MiUTR3H-07413 | CXCL13 miRNA 3'UTR clone | Inquiry |
| AD04423Z | Human CXCL10 adenoviral particles | Inquiry |
| AD04425Z | Human CXCL12 adenoviral particles | Inquiry |
| AD04426Z | Human CXCL13 adenoviral particles | Inquiry |
| AD04430Z | Human CXCL2 adenoviral particles | Inquiry |
| AD04433Z | Human CXCL6 adenoviral particles | Inquiry |
The CXCL family members interact with various receptors to activate diverse signaling pathways and participate in numerous biological processes. Here is an overview of some key CXCL family members and their receptors:
| Chemokine | Receptor | Function |
| CXCL1 | CXCR2 | Recruits immune cells (particularly neutrophils); promotes inflammation, immune regulation, and angiogenesis. |
| CXCL2 | CXCR2 | Neutrophil chemotaxis. |
| CXCL3 | CXCR2 | Neutrophil chemotaxis. |
| CXCL4 | CXCR3B | Involved in hemostasis; stimulates immune cells at tumor sites. |
| CXCL5 | CXCR1/2 | Plays a role in immune responses and inflammation. |
| CXCL6 | CXCR1/2 | Neutrophil chemotaxis; affects cell permeability, apoptosis, and proliferation. |
| CXCL7 | CXCR2 | Secreted by monocytes and macrophages; promotes tumor progression. |
| CXCL8 | CXCR1/2 | Active angiogenic and pro-inflammatory factors; are involved in cancer development, tumor migration, and proliferation. |
| CXCL9 | CXCR3 | Recruits Th cells, T cells, and natural killer cells; contributes to anti-infection and anti-tumor effects. |
| CXCL10 | CXCR3 | Similar functions to CXCL9 and CXCL11. |
| CXCL11 | CXCR3 | Similar functions to CXCL9 and CXCL10. |
| CXCL12 | CXCR4/7 | Has angiogenic properties; regulates tumor progression. |
| CXCL13 | CXCR3/5 | Effective B cell chemokine; involved in cancer progression. |
| CXCL14 | CXCR4 | Involved in immune cell infiltration, cell mobilization, and dendritic cell maturation; affects tumor progression differently depending on the source. |
| CXCL16 | CXCR6 | Recruits natural killer cells; expressed in organs like the liver, lung, and kidney; combats tumors. |
| CXCL17 | CXCR8 | Produced by airway epithelium; involved in various cancers, recruits monocytes and macrophages, inhibits pathogens, and is involved in tumor angiogenesis. |
In biological processes, the CXCL family regulates not only leukocyte migration but also tumor growth and development. Extensive research has confirmed that the CXCL family is involved in regulating:
1. Immune Cell Activity: Members recruit and activate various immune cells, including neutrophils, T cells, and B cells, thus modulating immune responses.
2. Tumor Cell Proliferation, Invasion, and Metastasis: Several CXCL family members are known to either promote or inhibit tumor cell growth and spread.
3. Tumor Microvessel Formation: Certain CXCL family members, especially those in the ELR+ subgroup, can enhance angiogenesis, providing the necessary blood supply for tumor growth.
4. Tumor Cell Transformation: CXCL family members may be involved in the conversion of normal cells to tumor cells.
5. Altered Angiogenic Environments: By modulating the expression of angiogenesis-related factors, CXCL family members can influence local microenvironments and vascular formation.
6. Promotion of Local Tumor Cell Growth: Some CXCL family members can directly stimulate tumor cell proliferation.
7. Extracellular Matrix and Basement Membrane Invasion: CXCL family members might participate in the degradation of the extracellular matrix, facilitating tumor cell invasion and metastasis.
8. Distant Organ Metastasis: Certain CXCL family members can guide tumor cells to specific organs.
9. Stem Cell Migration: CXCL family members like CXCL12 are crucial in stem cell chemotaxis and migration, vital for wound healing and tissue repair.
Figure 1. The roles of the CXCL family in cancer. (Zhou C, et al., 2023)
These biological actions are closely linked to the development and progression of various diseases, including inflammation, immune disorders, and cancer.
In clinical applications, the CXCL family holds significant promise due to its critical role in diverse diseases:
1. Biomarkers: Several CXCL family members serve as diagnostic, prognostic, or disease activity biomarkers. For instance, CXCL8 might be used as a diagnostic marker for non-small cell lung cancer, while CXCL10 could indicate disease activity in systemic lupus erythematosus.
2. Therapeutic Targets: Drugs targeting CXCL family members or their receptors are under development for treating cancer, inflammatory diseases, and autoimmune conditions. Blocking the CXCL10-CXCR3 pathway may offer a new strategy for treating type 1 diabetes.
3. Predicting Treatment Response: Expression levels of certain CXCL family members may predict patient responses to specific treatments, which is crucial for personalized medicine.
4. Immunotherapy: In cancer immunotherapy, CXCL family members may enhance immune cell recognition and destruction of tumors.
5. Tissue Repair: Leveraging the role of CXCL family members like CXCL12 in stem cell migration may lead to new strategies for tissue repair and regeneration.
In conclusion, the CXCL family of chemokines represents a crucial element in the regulation of numerous physiological and pathological processes. Their extensive involvement in immune responses, tumor progression, and tissue repair highlights their potential as valuable biomarkers and therapeutic targets. As research continues to uncover the complexities of CXCL functions and interactions, their clinical applications are poised to advance, offering new opportunities for diagnosis, treatment, and personalized medicine.
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