Journal article
Ethanol Promotes Mammary Tumor Growth and Angiogenesis: the Involvement of Chemoattractant Factor MCP-1
Breast cancer research and treatment, Vol.133(3), pp.1037-1048
06/2012
DOI: 10.1007/s10549-011-1902-7
PMCID: PMC3323664
PMID: 22160640
Abstract
Alcohol consumption is a risk factor for breast cancer in humans. Experimental studies indicate that alcohol exposure promotes malignant progression of mammary tumors. However, the underlying cellular and molecular mechanisms remain unclear. Alcohol induces a pro-inflammatory response by modulating the expression of cytokines and chemokines. Monocyte chemoattractant protein-1 (MCP-1), also known as chemokine (C-C motif) ligand 2 (CCL2), is a pro-inflammatory chemokine implicated in breast cancer development/malignancy. We investigated the role of MCP-1 in alcohol-promoted mammary tumor progression. Using a xenograft model, we demonstrated that alcohol increased tumor angiogenesis and promoted growth/metastasis of breast cancer cells in C57BL/6 mice. Alcohol up-regulated the expression of MCP-1 and its receptor CCR2 in breast cancer cells
in vitro
and
in vivo
. Using a three-dimensional (3-D) tumor/endothelial cell co-culture system, we demonstrated MCP-1 regulated tumor/endothelial cell interaction and promoted tumor angiogenesis. More importantly, MCP-1 mediated alcohol-promoted angiogenesis; an antagonist of the MCP-1 receptor CCR2 significantly inhibited alcohol-stimulated tumor angiogenesis. The CCR2 antagonist abolished ethanol-stimulated growth of mammary tumors in mice. We further demonstrated that MCP-1 enhanced the migration, but not the proliferation of endothelial cells as well as breast cancer cells. These results suggest that MCP-1 plays an important role in ethanol-stimulated tumor angiogenesis and tumor progression.
Details
- Title: Subtitle
- Ethanol Promotes Mammary Tumor Growth and Angiogenesis: the Involvement of Chemoattractant Factor MCP-1
- Creators
- Siying Wang - Anhui Medical UniversityMei Xu - University of KentuckyFeifei Li - Anhui Medical UniversityXin Wang - University of KentuckyKimberly A Bower - University of KentuckyJacqueline A Frank - University of KentuckyYanmin Lu - Anhui Medical UniversityGang Chen - University of KentuckyZhuo Zhang - University of KentuckyZunji Ke - Chinese Academy of SciencesXianglin Shi - University of KentuckyJia Luo - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Breast cancer research and treatment, Vol.133(3), pp.1037-1048
- DOI
- 10.1007/s10549-011-1902-7
- PMID
- 22160640
- PMCID
- PMC3323664
- NLM abbreviation
- Breast Cancer Res Treat
- ISSN
- 0167-6806
- eISSN
- 1573-7217
- Language
- English
- Date published
- 06/2012
- Academic Unit
- Pathology
- Record Identifier
- 9984201248102771
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