PMID- 26014148
OWN - NLM
STAT- MEDLINE
DCOM- 20160921
LR  - 20181113
IS  - 1098-2744 (Electronic)
IS  - 0899-1987 (Print)
IS  - 0899-1987 (Linking)
VI  - 55
IP  - 5
DP  - 2016 May
TI  - Role of MCP-1 in alcohol-induced aggressiveness of colorectal cancer cells.
PG  - 1002-11
LID - 10.1002/mc.22343 [doi]
AB  - Epidemiological studies demonstrate that alcohol consumption is associated with 
      an increased risk of colorectal cancer (CRC). In addition to promoting 
      carcinogenesis, alcohol may also accelerate the progression of existing CRC. We 
      hypothesized that alcohol may enhance the aggressiveness of CRC. In this study, 
      we investigated the effect of alcohol on the migration/invasion and metastasis of 
      CRC. Alcohol increased the migration/invasion of colorectal cancer cells (DLD1, 
      HCT116, HT29, and SW480) in a concentration-dependent manner. Among these colon 
      cancer cell lines, HCT116 cells were most responsive while HT29 cells were the 
      least responsive to ethanol-stimulated cell migration/invasion. These in vitro 
      results were supported by animal studies which demonstrated that ethanol enhanced 
      the metastasis of colorectal cancer cells to the liver and lung. Monocyte 
      chemoattractant protein-1 (MCP-1) is a chemokine that plays an important role in 
      regulating tumor microenvironment and metastasis. Alcohol increased the 
      expression of MCP-1 and its receptor CCR2 at both protein and mRNA levels. The 
      pattern of alcohol-induced alterations in MCP-1 expression was consistent with 
      its effect on migration/invasion; HCT116 cells displayed the highest 
      up-regulation of MCP-1/CCR2 in response to alcohol exposure. An antagonist of 
      CCR2 blocked alcohol-stimulated migration. Alcohol caused an initial cytosolic 
      accumulation of beta-catenin and its subsequent nuclear translocation by inhibiting 
      GSK3beta activity. Alcohol stimulated the activity of MCP-1 gene promoter in a 
      beta-catenin-dependent manner. Furthermore, knock-down of MCP-1/CCR2 or beta-catenin 
      was sufficient to inhibit alcohol-induced cell migration/invasion. Together, 
      these results suggested that alcohol may promote the metastasis of CRC through 
      modulating GSK3beta/beta-catenin/MCP-1 pathway.
CI  - (c) 2015 Wiley Periodicals, Inc.
FAU - Xu, Mei
AU  - Xu M
AD  - Department of Pharmacology and Nutritional Sciences, University of Kentucky 
      College of Medicine, Lexington, Kentucky.
FAU - Wang, Siying
AU  - Wang S
AD  - Department of Pharmacology and Nutritional Sciences, University of Kentucky 
      College of Medicine, Lexington, Kentucky.
AD  - Pathophysiological Department, School of Basic Medicine, Anhui Medical 
      University, Hefei, Anhui, China.
FAU - Qi, Yuanlin
AU  - Qi Y
AD  - Department of Pharmacology and Nutritional Sciences, University of Kentucky 
      College of Medicine, Lexington, Kentucky.
FAU - Chen, Li
AU  - Chen L
AD  - Pathophysiological Department, School of Basic Medicine, Anhui Medical 
      University, Hefei, Anhui, China.
FAU - Frank, Jacqueline A
AU  - Frank JA
AD  - Department of Pharmacology and Nutritional Sciences, University of Kentucky 
      College of Medicine, Lexington, Kentucky.
FAU - Yang, Xiuwei H
AU  - Yang XH
AD  - Department of Pharmacology and Nutritional Sciences, University of Kentucky 
      College of Medicine, Lexington, Kentucky.
FAU - Zhang, Zhuo
AU  - Zhang Z
AD  - Graduate Center for Toxicology, University of Kentucky College of Medicine, 
      Lexington, Kentucky.
FAU - Shi, Xianglin
AU  - Shi X
AD  - Graduate Center for Toxicology, University of Kentucky College of Medicine, 
      Lexington, Kentucky.
FAU - Luo, Jia
AU  - Luo J
AD  - Department of Pharmacology and Nutritional Sciences, University of Kentucky 
      College of Medicine, Lexington, Kentucky.
LA  - eng
GR  - AA015407/AA/NIAAA NIH HHS/United States
GR  - R01 AA015407/AA/NIAAA NIH HHS/United States
GR  - R01 AA017226/AA/NIAAA NIH HHS/United States
GR  - P30 CA177558/CA/NCI NIH HHS/United States
GR  - AA017226/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150525
PL  - United States
TA  - Mol Carcinog
JT  - Molecular carcinogenesis
JID - 8811105
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Chemokine CCL2/*genetics/*metabolism
MH  - Colorectal Neoplasms/genetics/metabolism/*pathology
MH  - Ethanol/*pharmacology
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - HCT116 Cells
MH  - HT29 Cells
MH  - Humans
MH  - Mice
MH  - Neoplasm Metastasis
MH  - Neoplasm Transplantation
MH  - Promoter Regions, Genetic/drug effects
MH  - Receptors, CCR2/genetics/metabolism
MH  - Wnt Signaling Pathway/drug effects
PMC - PMC4659775
MID - NIHMS689468
OTO - NOTNLM
OT  - Chemokines
OT  - Wnt signaling
OT  - ethanol
OT  - metastasis
OT  - tumor promotion
EDAT- 2015/05/28 06:00
MHDA- 2016/09/23 06:00
PMCR- 2017/05/01
CRDT- 2015/05/28 06:00
PHST- 2015/01/08 00:00 [received]
PHST- 2015/04/27 00:00 [revised]
PHST- 2015/05/01 00:00 [accepted]
PHST- 2015/05/28 06:00 [entrez]
PHST- 2015/05/28 06:00 [pubmed]
PHST- 2016/09/23 06:00 [medline]
PHST- 2017/05/01 00:00 [pmc-release]
AID - 10.1002/mc.22343 [doi]
PST - ppublish
SO  - Mol Carcinog. 2016 May;55(5):1002-11. doi: 10.1002/mc.22343. Epub 2015 May 25.