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

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

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.

Original languageEnglish
Pages (from-to)1037-1048
Number of pages12
JournalBreast Cancer Research and Treatment
Volume133
Issue number3
DOIs
StatePublished - Jun 2012

Bibliographical note

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

Keywords

  • Alcohol
  • Angiogenesis
  • Chemokines
  • Metastasis
  • Migration

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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