title: Alcohol promotes mammary tumor growth through activation of VEGF-dependent tumor angiogenesis.
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 cellsin vitroandin 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 growthin vivo. These results indicate that alcohol may promote mammary tumor growth by stimulating VEGF-dependent angiogenesis.
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei, Anhui 230032, P.R. China ; Department of Hepatobiliary Surgery, Clinical Nutrition Center, Clinical Nutrition and Metabolism Key Laboratory, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Ni
authors.affiliation: Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Jinlian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Ji
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Luo
authors.affiliation: 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.
authors.forename: Siying
authors.initials: S
authors.lastname: Wang
keywords: alcohol; angiogenesis; breast cancer; endothelial cells