Breast Cancer Research and Treatment

, Volume 133, Issue 3, pp 1037–1048 | Cite as

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

  • 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
Preclinical Study

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.

Keywords

Alcohol Angiogenesis Chemokines Metastasis Migration 

Abbreviations

AMVD

Average microvessel density

CCL2

Chemokine (C–C motif) ligand 2

CCR2

CC chemokine receptor 2

CCR2A

CCR2 antagonist

MCP-1

Monocyte chemoattractant protein-1

Notes

Acknowledgment

This research is supported by grants from National Institute of Health (AA017226 and AA015407).

Conflict of interest

The authors declare that they have no conflict of interests.

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Siying Wang
    • 1
    • 2
  • Mei Xu
    • 1
  • Feifei Li
    • 2
  • Xin Wang
    • 3
  • Kimberly A. Bower
    • 1
  • Jacqueline A. Frank
    • 1
  • Yanmin Lu
    • 2
  • Gang Chen
    • 1
  • Zhuo Zhang
    • 3
  • Zunji Ke
    • 4
  • Xianglin Shi
    • 3
  • Jia Luo
    • 1
  1. 1.Department of Internal MedicineUniversity of Kentucky College of MedicineLexingtonUSA
  2. 2.Pathophysiological Department, School of Basic MedicineAnhui Medical UniversityHefeiChina
  3. 3.Graduate Center for ToxicologyUniversity of KentuckyLexingtonUSA
  4. 4.Institute for Nutritional Sciences, Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina

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