PMID- 22160640
OWN - NLM
STAT- MEDLINE
DCOM- 20121106
LR  - 20211021
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 133
IP  - 3
DP  - 2012 Jun
TI  - Ethanol promotes mammary tumor growth and angiogenesis: the involvement of 
      chemoattractant factor MCP-1.
PG  - 1037-48
LID - 10.1007/s10549-011-1902-7 [doi]
AB  - 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.
FAU - Wang, Siying
AU  - Wang S
AD  - Department of Internal Medicine, University of Kentucky College of Medicine, 130 
      Health Sciences Research Building, 1095 Veterans Drive, Lexington, KY 40536, USA. 
      sywang@ahmu.edu.cn
FAU - Xu, Mei
AU  - Xu M
FAU - Li, Feifei
AU  - Li F
FAU - Wang, Xin
AU  - Wang X
FAU - Bower, Kimberly A
AU  - Bower KA
FAU - Frank, Jacqueline A
AU  - Frank JA
FAU - Lu, Yanmin
AU  - Lu Y
FAU - Chen, Gang
AU  - Chen G
FAU - Zhang, Zhuo
AU  - Zhang Z
FAU - Ke, Zunji
AU  - Ke Z
FAU - Shi, Xianglin
AU  - Shi X
FAU - Luo, Jia
AU  - Luo J
LA  - eng
GR  - AA015407/AA/NIAAA NIH HHS/United States
GR  - R01 AA015407/AA/NIAAA NIH HHS/United States
GR  - R01 AA017226/AA/NIAAA NIH HHS/United States
GR  - R01 AA017226-05/AA/NIAAA NIH HHS/United States
GR  - AA017226/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20111209
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/genetics/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Coculture Techniques
MH  - Ethanol/*pharmacology
MH  - Female
MH  - Human Umbilical Vein Endothelial Cells/drug effects/metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neoplasm Metastasis
MH  - Neovascularization, Pathologic/genetics/*metabolism
MH  - Receptors, CCR2/antagonists & inhibitors/genetics/metabolism
MH  - Transplantation, Heterologous
MH  - Tumor Burden/drug effects
PMC - PMC3323664
MID - NIHMS344848
COIS- Conflict of interests: The authors declare that they have no conflict of 
      interests.
EDAT- 2011/12/14 06:00
MHDA- 2012/11/07 06:00
PMCR- 2013/06/01
CRDT- 2011/12/14 06:00
PHST- 2011/10/11 00:00 [received]
PHST- 2011/11/24 00:00 [accepted]
PHST- 2011/12/14 06:00 [entrez]
PHST- 2011/12/14 06:00 [pubmed]
PHST- 2012/11/07 06:00 [medline]
PHST- 2013/06/01 00:00 [pmc-release]
AID - 10.1007/s10549-011-1902-7 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2012 Jun;133(3):1037-48. doi: 10.1007/s10549-011-1902-7. 
      Epub 2011 Dec 9.