Role of MCP-1 in alcohol-induced aggressiveness of colorectal cancer cells

Mei Xu; Siying Wang; Yuanlin Qi; Li Chen; Jacqueline A Frank; Xiuwei H Yang; Zhuo Zhang; Xianglin Shi; Jia Luo

doi:10.1002/mc.22343

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Role of MCP-1 in alcohol-induced aggressiveness of colorectal cancer cells

Journal article

Peer reviewed

Role of MCP-1 in alcohol-induced aggressiveness of colorectal cancer cells

Mei Xu, Siying Wang, Yuanlin Qi, Li Chen, Jacqueline A Frank, Xiuwei H Yang, Zhuo Zhang, Xianglin Shi and Jia Luo

Molecular carcinogenesis, Vol.55(5), pp.1002-1011

05/2016

DOI: 10.1002/mc.22343

PMCID: PMC4659775

PMID: 26014148

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https://www.ncbi.nlm.nih.gov/pmc/articles/4659775View

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Abstract

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 β-catenin and its subsequent nuclear translocation by inhibiting GSK3β activity. Alcohol stimulated the activity of MCP-1 gene promoter in a β-catenin-dependent manner. Furthermore, knock-down of MCP-1/CCR2 or β-catenin was sufficient to inhibit alcohol-induced cell migration/invasion. Together, these results suggested that alcohol may promote the metastasis of CRC through modulating GSK3β/β-catenin/MCP-1 pathway.

Animals

Cell Line, Tumor

Cell Movement - drug effects

Chemokine CCL2 - genetics

Chemokine CCL2 - metabolism

Colorectal Neoplasms - genetics

Colorectal Neoplasms - metabolism

Colorectal Neoplasms - pathology

Ethanol - pharmacology

Gene Expression Regulation, Neoplastic - drug effects

HCT116 Cells

HT29 Cells

Humans

Mice

Neoplasm Metastasis

Neoplasm Transplantation

Promoter Regions, Genetic - drug effects

Receptors, CCR2 - genetics

Receptors, CCR2 - metabolism

Wnt Signaling Pathway - drug effects

Details

Title: Subtitle: Role of MCP-1 in alcohol-induced aggressiveness of colorectal cancer cells
Creators: Mei Xu - University of Kentucky
Siying Wang - Anhui Medical University
Yuanlin Qi - University of Kentucky
Li Chen - Anhui Medical University
Jacqueline A Frank - University of Kentucky
Xiuwei H Yang - University of Kentucky
Zhuo Zhang - University of Kentucky
Xianglin Shi - University of Kentucky
Jia Luo - University of Kentucky
Resource Type: Journal article
Publication Details: Molecular carcinogenesis, Vol.55(5), pp.1002-1011
DOI: 10.1002/mc.22343
PMID: 26014148
PMCID: PMC4659775
NLM abbreviation: Mol Carcinog
ISSN: 0899-1987
eISSN: 1098-2744
Grant note: AA015407 / NIAAA NIH HHS P30 CA177558 / NCI NIH HHS AA017226 / NIAAA NIH HHS R01 AA015407 / NIAAA NIH HHS R01 AA017226 / NIAAA NIH HHS
Language: English
Date published: 05/2016
Academic Unit: Pathology
Record Identifier: 9984201254302771

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