CXCR2 Gene Editing    

The chemokine receptors belong to the class A GPCRs and are mainly expressed in immune microenvironment. Chemokine system plays an important role in cell migration, development of immune cells and organs, inflammatory response, immune response process, pathogen infection, wound repair, and tumor formation/metastasis. There are more than 20 chemokine receptors together with about 50 chemokines in human body constituting the mechanistic chemokine system. CXCR2 is mainly expressed in monocytes, neutrophils, natural killer cells, endothelial cells, and mast cells, and is the receptor for CXC chemokine ligands, especially CXCL8. It has been shown that CXCR2 is phosphorylated by GPCR kinases after activation, which triggers dynamin-mediated and clathrin-mediated receptor internalization mediated by β-arrestin1/2 and AP-2. Activated CXCR2 induces calcium release, activation of the Ras/MAPK, and PI3K signaling cascades, and it participated in many immune responses including directed neutrophil migration.

CXCR2 and Cancer

Chemokines have been shown to regulate the inflammatory response in various tumor types. The host immune response regulates tumor growth and progression via favorable host homeostatic mechanisms, and may inhibit cancer metastasis by stimulating migration and interrupting these mechanisms. It is known that CXCR2 and its ligands are pro-inflammatory and angiogenic, supporting tumor growth and metastasis in an autocrine and paracrine manner. Importantly the ligands, CXCL8 and CXCL1, have been observed to influence breast tumor growth, chemoresistance and metastasis. Besides, CXCR2 expressed by endothelial cells binds to its angiogenic ELR⁺ (Glu-Leu-Arg) ligands secreted by tumor cells and promotes angiogenesis in breast tumors. Similarly, neutrophils, myeloid suppressor cells (MDSC) and bone marrow-derived myeloid cells (BMDCs) express CXCR2 and aid in tumor growth.

The importance of CXCR2 in tumorigenesis has been highly emphasized. ELR⁺ CXC chemokines are known to mediate their angiogenic effects through the CXCR2 receptor, and indeed its inhibition has shown several antitumorigenic effects. This provides the opportunity to intervene in key processes in tumor development, including growth, angiogenesis, invasion and metastasis. Inhibition of CXCL8 signalling in prostate cancer cells by the CXCR2 inhibitor, AZ10397767 can increase the cytotoxicity of 5-FU, which is a key anti-metabolite in solid-tumor chemotherapy. In breast cancer, malignant cells surviving initial chemo- and radiation therapy have higher expression of CXCR2 ligands. Knocking down CXCR2 increased the toxicity of chemotherapy agents paclitaxel and doxorubicin. It also enhanced paclitaxel antitumor activity in an in vivo breast cancer model. Compared to control animals, spontaneous lung metastases in animals with CXCR2 knockdown and treated with paclitaxel were significantly reduced. In addition, a study investigated the involvement of CXCL8 and CXCR2 in a 5-FU chemoresistant colorectal cell line (HCT116/5-FU), and found that both were upregulated in comparison to their chemosensitive parental cell line (HCT116). Inhibiting CXCR2 resulted in reduced cell proliferation in both cell lines. These examples highlight the importance of CXCR2 in chemotherapy resistance and provide evidence that targeting CXCR2 signalling can enhance the antitumor and antimetastatic activity of chemotherapeutic drugs.

CXCR2 Gene Editing Services

CRISPR/Cas9 Platform^CB, one of the leading biotechnological companies specializing in gene editing, is dedicated to offering comprehensive CRISPR/Cas9 gene-editing services to a wide range of genomics researchers. Based on our platform, we can help you effectively CXCR2 gene deleted, inserted or point mutated in cells or animals by CRISPR/Cas9 technology.

• CXCR2 Gene Knockout: We offer CXCR2 gene knockout cell line and knockout animal model generation service with high quality. Typically, we develop CRISPR-mediated gene editing cell lines including HEK239T, Hela, HepG2, U87, but we can use other cell lines according to your requirements. Our one-stop KO animal model generation service covers from sgRNA design and construction, pronuclear microinjection to Founders genotyping and breeding.
• CXCR2 Gene Knockin: CRISPR/Cas9 Platform^CB provides the one-stop CXCR2 knock-in cell line and knockout animal model generation services, including point mutation and gene insertion. Our expert staff has succeeded in dozens of CXCR2 knock-in cell line generation projects, including stem cells, tumor cells and even difficult-to-handle cells. We also have extensive experience in incorporating CRISPR/Cas9 technology into animal models, which have been fully recognized by our clients.

If you have any questions, please feel free to contact us.

Related Products at CRISPR/Cas9 Platform^CB

References

1. Sharma B, et al. Host Cxcr2-dependent regulation of mammary tumor growth and metastasis. Clinical & experimental metastasis, 2015, 32(1): 65-72.
2. Jaffer T, Ma D. The emerging role of chemokine receptor CXCR2 in cancer progression. Transl Cancer Res, 2016, 5(Suppl 4): S616-S28.
3. Zhang X, et al. The role of CXCR2 in acute inflammatory responses and its antagonists as anti-inflammatory therapeutics. Current opinion in hematology, 2019, 26(1): 28.
4. Liu K, et al. Structural insights into the activation of chemokine receptor CXCR2. The FEBS Journal, 2022, 289(2): 386-393.