CXCR2 Membrane Protein Introduction

Introduction of CXCR2

CXCR2, also known as Interleukin 8 receptor, belongs to a subfamily of chemokine receptors from a large family of G protein-coupled receptor, encoded by CXCR2 gene. It is one of seven CXC chemokine receptors (CXCR1-CXCR7) in mammals. The receptors can recognize CXC chemokine that possesses an E-L-R amino acid motif. Recently, most studies have been made to investigate the CXCR2 role in the treatment of cancer.

Function of CXCR2 Membrane Protein

Interleukin-8 is a powerful neutrophil chemotactic factor, which can bind to CXCR2 with high affinity and transduce the signal through a G-protein-activated second messenger system. Moreover, chemokine (C-X-C motif) ligand 1 (CXCL1/MGSA) is a protein with melanoma growth stimulating activity, which can also bind to CXCR2 involved in regulation the serum-dependent melanoma cell growth. CXCR2 has multiple biological functions. It is involved in the mediation of neutrophil migration to sites of inflammation, as well as the angiogenic effects of IL8 in intestinal microvascular endothelial cells. Recent studies also revealed that CXCR2 may be associated with proliferation, angiogenesis, invasion, migration, and resistance to drugs of the tumors. The overexpression of CXCR2 is correlated to poor overall and disease-free survival in metastatic colorectal cancer, laryngeal squamous cell carcinoma, lung cancer, pancreatic ductal carcinoma, clear-cell renal cell carcinoma and hepatocellular carcinoma, suggesting that CXCR2 overexpression may be a deteriorative indicator of cancer.

Fig.1 Schematic diagram illustrating the principal signaling pathways activated by IL-8 and their relevance to cell survival. (Campbell, 2013)

Application of CXCR2 Membrane Protein in Literature

1. Cao Q., et al. Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice. Archives of Medical Science. 2018, 14(3): 635-644. PubMed ID ID: 29765453
   
   

   The study implicates that SB225002, the inhibitor of CXCR2, is a potential novel treatment for LPS-induced acute lung injury. It could improve LPS-induced acute lung injury in mice via reducing neutrophil recruitment and vascular permeability.

2. Qiao B., et al. The prognostic value of CXC chemokine receptor 2 (CXCR2) in cancers: a meta-analysis. Oncotarget. 2018, 9(19): 15068-15076. PubMed ID: 29599927
   
   

   The authors analyzed 2,461 patients with cancer from twelve studies using a meta-analysis. Results show that high CXCR2 levels are associated with poor overall survival (OS) and RFS in patients with laryngeal squamous cell carcinoma, lung cancer, pancreatic ductal carcinoma, clear-cell renal cell carcinoma and hepatocellular carcinoma, without in digestive tract cancer. Hence CXCR2 is a poor prognostic marker in patients with cancer except for digestive tract cancer.

3. He J T., et al. CXCL1 and CXCR2 as potential markers for vital reactions in skin contusions. Forensic Science Medicine & Pathology. 2018, 14(2): 174-179. PubMed ID: 29607464
   
   

   The study finds that CXCL1 and CXCR2 protein levels are no difference between wounded and intact skin using western blot analysis. However, the CXCL1 and CXCR2 mRNA levels are higher in contused mouse and human skin compared with intact skin. These suggest that the CXCL1 and CXCR2 mRNA levels in contused skin can be used as potential markers for a vital reaction in skin contusions.

4. Ignacio M C., et al. CXCR2 is a negative regulator of p21 in p53-dependent and independent manner via Akt-mediated Mdm2 in ovarian cancer. Oncotarget. 2018, 9(11): 9751-9765. PubMed ID: 29515768
   
   

   The study indicates that CXCR2 can promote ovarian cancer cell proliferation by suppressing p21 which is mediated via Akt-Mdm2 signaling in p53-dependent and independent manner.

5. Wu S., et al. CXCR1/2 chemokine network regulates melanoma resistance to chemotherapies mediated by NF-kB. Current Molecular Medicine. 2017, 17(6): 436-449. PubMed ID: 29256349
   
   

   The study reveals that the higher levels of CXCL8 and CXCR2 are detected in melanoma cell line chronically exposed to chemotherapeutic drug dacarbazine compared with parent cells. These suggest that CXCL8 and CXCR2 levels can act as a signature of drug resistance.

CXCR2 Preparation Options
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Reference

1. Campbell L M., et al. (2013). Rationale and Means to Target Pro-Inflammatory Interleukin-8 (CXCL8) Signaling in Cancer. Pharmaceuticals, 6(8): 929-59.

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