Alcohol promotes mammary tumor growth through activation of VEGF‑dependent tumor angiogenesis

Lu,Yanmin; Ni,Fang; Xu,Mei; Yang,Jinlian; Chen,Ji; Chen,Zhuo; Wang,Xinyi; Luo,Jia; Wang,Siying

doi:10.3892/ol.2014.2146

Alcohol promotes mammary tumor growth through activation of VEGF‑dependent tumor angiogenesis

Authors:
- Yanmin Lu
- Fang Ni
- Mei Xu
- Jinlian Yang
- Ji Chen
- Zhuo Chen
- Xinyi Wang
- Jia Luo
- Siying Wang
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Affiliations: Department of Pathophysiology, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, KY 40536, USA
Published online on: May 16, 2014 https://doi.org/10.3892/ol.2014.2146
Pages: 673-678

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Abstract

Alcohol consumption has been recognized as a risk factor for breast cancer. Experimental studies demonstrate that alcohol exposure promotes the progression of existing mammary tumors. However, the mechanisms underlying this effect remain unclear. In the present study, the role of vascular endothelial growth factor (VEGF) in alcohol promotion of breast cancer development was investigated using a mouse xenograft model of mammary tumors and a three‑dimensional (3D) tumor/endothelial cell co‑culture system. For the mouse xenograft model, mouse E0771 breast cancer cells were implanted into the mammary fat pad of C57BL6 mice. These mice were exposed to alcohol in their drinking water. For the 3D co‑culture system, E0771 cells and MDA‑MB231 breast cancer cells were co‑cultured with SVEC4‑10EE2 and human umbilical vein endothelial cells, respectively. The results demonstrated that alcohol increased tumor angiogenesis and accelerated tumor growth. Furthermore, it appeared that alcohol induced VEGF expression in breast cancer cells in vitro and in vivo. Blocking VEGF signaling by SU5416 inhibited tumor angiogenesis in the 3D tumor/endothelial cell co‑culture system. Furthermore, injection of SU5416 into mice inhibited alcohol‑promoted mammary tumor growth in vivo. These results indicate that alcohol may promote mammary tumor growth by stimulating VEGF‑dependent angiogenesis.

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