Review
Copyright ©2013 Baishideng Publishing Group Co.
World J Gastroenterol. May 21, 2013; 19(19): 2847-2863
Published online May 21, 2013. doi: 10.3748/wjg.v19.i19.2847
Table 1 Ligand specificity of chemokine receptors implicated in gastrointestinal disease
CC-chemokinesCXC-chemokinesCX3C-chemokine
Ligands
Receptors
Ligands
Receptors
Ligands
Receptors
CCL2CCR2CXCL1CXCR2/CXCR1CX3CL1CX3CR1
CCL3CCR1/CCR5CXCL2CXCR2
CCL4CCR5CXCL4L1CXCR3
CCL5CCR1/CCR3/CCR5CXCL5CXCR2
CCL7CCR1/CCR2/CCR3CXCL7CXCR2
CCL8CCR3/CCR5CXCL8CXCR1
CCL13CCR2/CCR3CXCL9CXCR3
CCL19CCR7CXCL10CXCR3
CCL20CCR6CXCL11CXCR3
CCL21CCR7CXCL12CXCR4/R7
CCL25CCR9CXCL14Unknown
CCL27CCR10CXCL17Unknown
Table 2 Chemokines/chemokine receptors in this table appear sequentially according to their description in this review
OrganChemokines and receptorsPossible role/observed phenomenon
Oral cavityCXCL1Angiogenic activity[103]
CXCL8Proliferation, metastasis, tumor development and the induction of inflammation in periodontal disease[60,104-106]
CXCL5Proliferation, cell motility and invasion[107]
CXCR4Enhancement of invasiveness[108]
CXCL12Upregulation in metastasis[109]
CCR6, CCR7Involvement in metastatic activity[110]
CCR7Enhancement of invasion[111]
CCL20Upregulated with bacterial infection in OSCC cell lines[152]
EsophagusCXCL8Possible index of inflammation, upregulation in cancer-related cachexia[113,114]
CXCR4Positive regulator of HER[116]
StomachCXCL12, CXCR4Metastasis through activation of AKT-mTOR pathway and MMPs, upregulation in lymph node metastasis, strong correlation with tumor development[117,118,124]
CXCR4Enhancement of metastasis through p38 signaling pathway[119]
CXCL12Acquisition of invasive/metastatic phenotype, enhancement of proliferation when coexpressed with other molecules[120,123]
CXCL1Activation of lymphangiogenesis by stimulating LECs[126]
CXCR2Strong correlation with TNM staging and lymphatic vessel density[127-130]
CXCL8Enhancement of tumor development factors, and a possible risk factor as mutant, association with angiogenesis, development of gastric adenocarcinoma[132-134,183]
CXCL5Marker for late stage gastric cancer[137]
Other candidatesCC-chemokines (CCL2, 3, 5, 21, 25)/CXC-chemokines (1, 7, 8, 12, 14)/CCR6[139]
LiverCXCR4Metastasis, upregulation in PVTT[142-143]
CXCR2Upregulation in HCC, especially in late stage[128]
CCL2Application to prevent metastasis, application to prevent HCC by deactivating AKT pathway[144-147]
CXCR7Upregulation in HCC, functional in tumor development and angiogenesis but not in metastasis[148-149]
CXCL12, CXCR4Enhancement of tumor cell extravasation through upregulation of Rho/Rac/Cdc42[150]
CCR6Upregulation in metastasis[153]
CCL20Enhanced expression in HCC[155]
D6 receptorPrevention of liver injury[171]
PancreasCCL20Associated with tumor staging[154]
CCR6Upregulated in chronic pancreatitis, pancreatic cystadenoma and pancreatic carcinoma[154]
CXCL5, CXCL8Upregulation in metastatic pancreatic carcinoma[140]
CXCL5Correlated with poorer tumor differentiation, advanced clinical stage, and shorter patient survival, and ERK, AKT and STAT mediated angiogenesis[156]
CXCL8, CXCR1/2Upregulation in adenocarcinomas and neuroendocrine tumors[157]
CXCL12, CXCR4Downregulation of CXCL12 and upregulation of CXCR4 in tumors. CXCL12 correlated with MVD but not with MLVD, while CXCR4 showed opposite pattern[158]
CXCR4, CXCR7CXCR7 associated with tumor grade, inversely associated with tumor size, and possibly associated with tumor progression and differentiation but not with CXCR4[159]
CX3CL1,CX3CR1Perineural invasion and dissemination of neoplastic cells along intra- and extra-pancreatic nerves[163,164]
CXCL17 (+ ICAM2)Diagnostic molecular marker[167]
CXCL7 (+ CA19-9)Diagnostic molecular marker[168]
ColonCXCL4L1Upregulation in colorectal cancer[115]
CCL2upregulation in mucosa of IBD[169]
D6 receptorPlays role of sequestering several chemokines (in mouse colitis model experiment), plays suppressive role in the development and growth of vascular tumors[170,172]
CCL2, CCR2important mediator in colon tumor development[173]
CXCL8Upregulation along with the development of Crohn's disease, affecting biological responses of human intestinal microvascular endothelial cells in colitis model, positvely correlated with earlier disease stage and improved relapse-free survival[164,175,180]
CXCL10, CXCL41Synergistic upregulation with CXCL8 by diverse stimuli, induction by ERK2 and PI-3K/AKT pathway via PAR2[175,178]
CCL20, CXCL1/2, CXCL8Remains high even after the treatment with anti-TNF antibody[179]
CXCL1, CXCR1/2Upregulation in stage II and III CRC, upregulation in stage II and III CRC[180]
CXCR3 pathwayCXCL9-pediatric Crohn’s disease, CXCL11-UC in all age groups[181]
Other chemokinesIL-17 affects CXCL8, CXCL1, CCL20, CXCL10, CXCL11 and CCR5 in colon cancer cells[182]