The CXC Chemokine family represents a unique group of cytokines that have the ability to function as either promotors or inhibitors of angiogenesis.CXC chemokines are characteristically heparin-binding proteins. On structural level, they have four highly conserved cysteine amino-acid residues.
An Overview of CXCR
CXC type chemokine receptor (CXCR) is a kind of chemokine receptors, which are members of the G protein-coupled receptor protein family with 7 transmembrane structures. Chemokines belong to a small molecule cytokine protein family with a relative molecular mass of 8-10 x 103. CXCR is expressed not only on the surface of inflammatory cells such as macrophages and neutrophils, but also in tumor cells. In addition, CXCR plays an important role in tumor progression and metastasis.
Major type of CXCR
CXCR includes seven CXC-type chemokine receptors, CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, and CXCR7. CXCR1 gene is located on chromosome 2q35 and promotes the proliferation and metastasis of cancer cells. CXCR3 is a G protein-coupled chemokine receptor that is located on chromosome Xq13 and encodes 368 amino acids. CXCR3 is mainly expressed on the surface of activated T cells, which are also expressed in various malignant tumors, such as breast cancer, colon cancer and gastric cancer. CXCR4 gene is located on chromosome 2q21 and consists of 352 amino acids. High expression of CXCR4 is associated with tumor invasion and poor tumor prognosis. CXCR7 can be expressed on the surface of activated endothelial cells, lymphocytes, fetal liver cells and the like, while CXCR7 is overexpressed in gastric cancer. CXCR2 and CXCR6 play important roles in tumor invasion and metastasis. Down-regulation of CXCR2 expression reduced the expression of Ets-1, SRC-1, and JNK proteins and the phosphorylation of c-Jun and ERK1/2, thereby inhibiting the invasion and metastasis of tumor cells. Blocking CXCR6 expression can block Akt pathway and down-regulate MMP-9 (matrix metalloprotein-9) expression, and inhibit tumor cell metastasis and invasion.
Inhibition of CXCR
In vitro experiments have shown that the small molecule inhibitors AMD3100, 12G5 monoclonal antibodies can inhibit the CXCL12/CXCR4 axis, thereby inhibiting the growth and invasion of gastric cancer cells. CXCR inhibitors may have a good application prospect in cancer treatment in the future.
CXCR and diseases
Based on the above description of various types of CXCR, regulation of CXCR may be a strategy for cancer-specific treatment. In the future, CXCR can not only assist cancer diagnosis and judge the prognosis of patients, but also become the intervention target of CXCR biotherapy.
Li Z, Wang Y., Dong S., et al. (2014) Association of CXCR1 and 2 expressions with gastric cancer metastasis in ex vivo and tumor cell invasion in vitro. Cytokine, 69(1): 6-13.
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