Table 1.
Chemokine-Receptor Axis |
Importance in CNS Tumors/Gliomas | Author |
---|---|---|
CXCL8-CXCR1/2 | CXCL8 expression at mRNA and protein level detected in glioma tissues |
[139,170] |
Increased expression of CXCL8 and CXCR2 in tumor samples from GBM patients than in normal brain tissue |
[174,188] | |
Correlation of CXCL8 and CXCR2 tumor expression with glioma grade and disease-free and overall survival in glioblastoma patients |
[174] | |
Concentrations of CXCL8 in sera and CSF significantly elevated in patients with CNS tumor compared to non-tumoral control group | [176,177] | |
CXCL8-CXCR2 interaction triggers tumor cells proliferation, migration of endothelial cells, and angiogenesis | [139,170,174,187] | |
Upregulation of CXCL8-CXCR2 axis in HGG tumors resistant to anti-angiogenic therapy | [183,184] | |
CXCL12-CXCR4 | Increased expression of CXCL12 and CXCR4 in various types of malignant CNS tumors | [199,200,201] |
High expression of CXCL12 and CXCR4 localized at the invasive edge and in the regions with high microvessel density, tumor necrosis, and apoptosis within glioblastoma tissue | [201,202,203] | |
CXCL12 induces a significant increase of DNA synthesis and chemotaxis in a primary human glioblastoma cell line | [204] | |
Correlation of increased CXCR4 expression with tumor grade | [201,207] | |
CXCL12 expression as prognostic factor of tumor progression in low-grade gliomas | [209] | |
CXCL12-CXCR4 axis participates in tumoral angiogenesis and promotes VEGF production by glioma | [210,211] | |
CXCL16-CXCR6 | Increased expression of CXCL16 and CXCR6 at mRNA and protein in human gliomas | [214,215] |
CXCL16-CXCR6 axis promotes human GBM cell growth, invasion, and migration | [215,217] | |
CXCL16-CXCR6 axis induces polarization of GAMs toward an anti-inflammatory/pro-tumor phenotype | [51] | |
CX3CL1-CX3CR1 | CX3CL1 and CX3CR1 expression at mRNA and protein level detected in glioma cells and various grades of glioma | [218,221] |
Correlation of CX3CL1 expression levels and glioma grade | [218] | |
CX3CL1 expression is a prognostic factor of glioma patients’ overall survival | [218] | |
Reduced tumor cell aggregation and increased glioma invasiveness as a result of CX3CL1 inhibition by monoclonal antibody |
[221] | |
CCL2-CCR2 | CCL2 secreted by glioma cells promotes tumor growth and migration of malignant cells | [227] |
Correlation of CCL2 expression with tumor grade and TAMs accumulation in GBM tumor mass and its surrounding |
[231] | |
Blocking of CCL2 with a neutralizing antibody reduced microglia/macrophages infiltrate in glioma and prolonged survival in mice |
[235] | |
CCL2-CCR2 axis promotes tumor progression by recruitment of suppressive MDSCs | [190,237] | |
CCL2 participates in macrophage-mediated angiogenic switch | [238,239] | |
Increased expression of CCR2 stimulates TAMs and fibroblasts recruitment at the primary tumors, enhance invasion, angiogenesis, and metastasis of glioma | [241] | |
CCL5-CCR5 | CCL5-CCR5 axis induces proliferation and invasive responses in glioblastoma cells | [242] |
High expression of CCR5 in GBM tissues correlates with poor prognosis for patients | [242] | |
Downregulation of CCR5 significantly inhibited tumor growth in mice model of glioma | [242] | |
Blocking of CCR5 prevents M2 microglia polarization and results in reduced microglia migration | [243] |