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01.06.2012 | Preclinical Study

Ethanol promotes mammary tumor growth and angiogenesis: the involvement of chemoattractant factor MCP-1

verfasst von: Siying Wang, Mei Xu, Feifei Li, Xin Wang, Kimberly A. Bower, Jacqueline A. Frank, Yanmin Lu, Gang Chen, Zhuo Zhang, Zunji Ke, Xianglin Shi, Jia Luo

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2012

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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, 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 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.

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Titel: Ethanol promotes mammary tumor growth and angiogenesis: the involvement of chemoattractant factor MCP-1
verfasst von: Siying Wang
Mei Xu
Feifei Li
Xin Wang
Kimberly A. Bower
Jacqueline A. Frank
Yanmin Lu
Gang Chen
Zhuo Zhang
Zunji Ke
Xianglin Shi
Jia Luo
Publikationsdatum: 01.06.2012
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2012
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-011-1902-7

Springer Medizin

Ethanol promotes mammary tumor growth and angiogenesis: the involvement of chemoattractant factor MCP-1

Abstract

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Springer Medizin

Abstract

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