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
Published online May 21, 2013. doi: 10.3748/wjg.v19.i19.2847
CC-chemokines | CXC-chemokines | CX3C-chemokine | |||
Ligands | Receptors | Ligands | Receptors | Ligands | Receptors |
CCL2 | CCR2 | CXCL1 | CXCR2/CXCR1 | CX3CL1 | CX3CR1 |
CCL3 | CCR1/CCR5 | CXCL2 | CXCR2 | ||
CCL4 | CCR5 | CXCL4L1 | CXCR3 | ||
CCL5 | CCR1/CCR3/CCR5 | CXCL5 | CXCR2 | ||
CCL7 | CCR1/CCR2/CCR3 | CXCL7 | CXCR2 | ||
CCL8 | CCR3/CCR5 | CXCL8 | CXCR1 | ||
CCL13 | CCR2/CCR3 | CXCL9 | CXCR3 | ||
CCL19 | CCR7 | CXCL10 | CXCR3 | ||
CCL20 | CCR6 | CXCL11 | CXCR3 | ||
CCL21 | CCR7 | CXCL12 | CXCR4/R7 | ||
CCL25 | CCR9 | CXCL14 | Unknown | ||
CCL27 | CCR10 | CXCL17 | Unknown |
Organ | Chemokines and receptors | Possible role/observed phenomenon |
Oral cavity | CXCL1 | Angiogenic activity[103] |
CXCL8 | Proliferation, metastasis, tumor development and the induction of inflammation in periodontal disease[60,104-106] | |
CXCL5 | Proliferation, cell motility and invasion[107] | |
CXCR4 | Enhancement of invasiveness[108] | |
CXCL12 | Upregulation in metastasis[109] | |
CCR6, CCR7 | Involvement in metastatic activity[110] | |
CCR7 | Enhancement of invasion[111] | |
CCL20 | Upregulated with bacterial infection in OSCC cell lines[152] | |
Esophagus | CXCL8 | Possible index of inflammation, upregulation in cancer-related cachexia[113,114] |
CXCR4 | Positive regulator of HER[116] | |
Stomach | CXCL12, CXCR4 | Metastasis through activation of AKT-mTOR pathway and MMPs, upregulation in lymph node metastasis, strong correlation with tumor development[117,118,124] |
CXCR4 | Enhancement of metastasis through p38 signaling pathway[119] | |
CXCL12 | Acquisition of invasive/metastatic phenotype, enhancement of proliferation when coexpressed with other molecules[120,123] | |
CXCL1 | Activation of lymphangiogenesis by stimulating LECs[126] | |
CXCR2 | Strong correlation with TNM staging and lymphatic vessel density[127-130] | |
CXCL8 | Enhancement of tumor development factors, and a possible risk factor as mutant, association with angiogenesis, development of gastric adenocarcinoma[132-134,183] | |
CXCL5 | Marker for late stage gastric cancer[137] | |
Other candidates | CC-chemokines (CCL2, 3, 5, 21, 25)/CXC-chemokines (1, 7, 8, 12, 14)/CCR6[139] | |
Liver | CXCR4 | Metastasis, upregulation in PVTT[142-143] |
CXCR2 | Upregulation in HCC, especially in late stage[128] | |
CCL2 | Application to prevent metastasis, application to prevent HCC by deactivating AKT pathway[144-147] | |
CXCR7 | Upregulation in HCC, functional in tumor development and angiogenesis but not in metastasis[148-149] | |
CXCL12, CXCR4 | Enhancement of tumor cell extravasation through upregulation of Rho/Rac/Cdc42[150] | |
CCR6 | Upregulation in metastasis[153] | |
CCL20 | Enhanced expression in HCC[155] | |
D6 receptor | Prevention of liver injury[171] | |
Pancreas | CCL20 | Associated with tumor staging[154] |
CCR6 | Upregulated in chronic pancreatitis, pancreatic cystadenoma and pancreatic carcinoma[154] | |
CXCL5, CXCL8 | Upregulation in metastatic pancreatic carcinoma[140] | |
CXCL5 | Correlated with poorer tumor differentiation, advanced clinical stage, and shorter patient survival, and ERK, AKT and STAT mediated angiogenesis[156] | |
CXCL8, CXCR1/2 | Upregulation in adenocarcinomas and neuroendocrine tumors[157] | |
CXCL12, CXCR4 | Downregulation of CXCL12 and upregulation of CXCR4 in tumors. CXCL12 correlated with MVD but not with MLVD, while CXCR4 showed opposite pattern[158] | |
CXCR4, CXCR7 | CXCR7 associated with tumor grade, inversely associated with tumor size, and possibly associated with tumor progression and differentiation but not with CXCR4[159] | |
CX3CL1,CX3CR1 | Perineural 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] | |
Colon | CXCL4L1 | Upregulation in colorectal cancer[115] |
CCL2 | upregulation in mucosa of IBD[169] | |
D6 receptor | Plays role of sequestering several chemokines (in mouse colitis model experiment), plays suppressive role in the development and growth of vascular tumors[170,172] | |
CCL2, CCR2 | important mediator in colon tumor development[173] | |
CXCL8 | Upregulation 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, CXCL41 | Synergistic upregulation with CXCL8 by diverse stimuli, induction by ERK2 and PI-3K/AKT pathway via PAR2[175,178] | |
CCL20, CXCL1/2, CXCL8 | Remains high even after the treatment with anti-TNF antibody[179] | |
CXCL1, CXCR1/2 | Upregulation in stage II and III CRC, upregulation in stage II and III CRC[180] | |
CXCR3 pathway | CXCL9-pediatric Crohn’s disease, CXCL11-UC in all age groups[181] | |
Other chemokines | IL-17 affects CXCL8, CXCL1, CCL20, CXCL10, CXCL11 and CCR5 in colon cancer cells[182] |
- Citation: Miyazaki H, Takabe K, Yeudall WA. Chemokines, chemokine receptors and the gastrointestinal system. World J Gastroenterol 2013; 19(19): 2847-2863
- URL: https://www.wjgnet.com/1007-9327/full/v19/i19/2847.htm
- DOI: https://dx.doi.org/10.3748/wjg.v19.i19.2847