PMID- 25346504
OWN - NLM
STAT- MEDLINE
DCOM- 20150721
LR  - 20211021
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Linking)
VI  - 38
IP  - 10
DP  - 2014 Oct
TI  - Ethanol supports macrophage recruitment and reinforces invasion and migration of 
      Lewis lung carcinoma.
PG  - 2597-606
LID - 10.1111/acer.12512 [doi]
AB  - BACKGROUND: Inflammation plays a critical role in cancer progression, and our 
      data suggested that ethanol (EtOH) could promote the progression of breast cancer 
      via increased monocyte chemo-attractant protein-1 (MCP-1). Thus, we investigated 
      the effects of EtOH on lung cancer growth and metastasis to explore whether 
      immunosuppression had a role. METHODS: C57BL/6 mice (n = 10) implanted with Lewis 
      lung cancer (LLC) cells were used to model physiologically relevant EtOH intake 
      on tumor growth and inflammation after macrophage polarization. Tumors were 
      isolated and measured, and MCP-1 expression was measured via immunohistochemistry 
      and Western blot. Recruitment of macrophages using CD11b and F4/80 antibodies was 
      detected with immunohistochemistry and flow cytometry. Changes in arginase I and 
      inducible nitric oxide synthase (iNOS) expression were measured with 
      immunofluorescent microscopy. EtOH's effect on in vitro tumor angiogenesis was 
      evaluated in culture, and the tumor microvessel density was assessed with CD31 
      immunohistochemistry. Matrix metalloproteinase 9 and interleukin 10 expressions 
      were measured by Western blot, ELISA, and immunohistochemistry. Finally, we 
      treated a macrophage cell line RAW264.7 with EtOH and measured changes in 
      arginase I and iNOS expression. RESULTS: With EtOH exposure, macrophage density 
      was positively correlated with MCP-1 expression. Macrophages infiltrated the 
      tumor site, becoming tumor-associated macrophages that polarized to M2 phenotypes 
      (ArgI(high) /iNOS(low) ) after EtOH treatment. Cancerous cells interacted with 
      immune cells, especially M2 macrophages, and promoted tumor angiogenesis, 
      progression, and invasiveness. RAW264.7 cells stimulated with EtOH expressed more 
      arginase I and less iNOS than controls. These results agreed with the features of 
      M2 phenotype macrophages (ArgI(high) /iNOS(low) ). CONCLUSIONS: Data show that 
      EtOH induced M2 phenotype macrophages, suggesting that progression and metastasis 
      of LLC may be mediated by recruitment of M2 macrophages, especially under the 
      influence of EtOH.
CI  - Copyright (c) 2014 by the Research Society on Alcoholism.
FAU - Yu, Keke
AU  - Yu K
AD  - Department of Biaobank, Shanghai Chest Hospital, Shanghai JiaoTong University, 
      Shanghai, China; Department of Pathophysiology, Anhui Medical University, Hefei, 
      Anhui, China; Department of Immunology, Anhui Medical University, Hefei, Anhui, 
      China.
FAU - Yang, Jinlian
AU  - Yang J
FAU - Wang, Fei
AU  - Wang F
FAU - Chen, Li
AU  - Chen L
FAU - Lu, Yanmin
AU  - Lu Y
FAU - Luo, Jia
AU  - Luo J
FAU - Wang, Siying
AU  - Wang S
LA  - eng
GR  - R01 AA017226/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 130068-27-8 (Interleukin-10)
RN  - 3K9958V90M (Ethanol)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.5.3.1 (Arg1 protein, mouse)
RN  - EC 3.5.3.1 (Arginase)
SB  - IM
MH  - Animals
MH  - Arginase/metabolism
MH  - Carcinoma, Lewis Lung/metabolism/*pathology
MH  - Cell Line
MH  - Cell Movement/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Chemokine CCL2/metabolism
MH  - Disease Models, Animal
MH  - Ethanol/*pharmacology
MH  - Female
MH  - Interleukin-10/metabolism
MH  - Lung Neoplasms/metabolism/*pathology
MH  - Macrophages/*drug effects/metabolism/*pathology
MH  - Male
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice, Inbred C57BL
MH  - Neoplasm Invasiveness/*pathology
MH  - Neovascularization, Pathologic/pathology
MH  - Nitric Oxide Synthase Type II/metabolism
OTO - NOTNLM
OT  - Ethanol
OT  - Lewis Lung Carcinoma
OT  - M2 Macrophages
OT  - Monocyte Chemo-Attractant Protein-1
OT  - Tumor-Associated Macrophages
EDAT- 2014/10/28 06:00
MHDA- 2015/07/22 06:00
CRDT- 2014/10/28 06:00
PHST- 2014/02/23 00:00 [received]
PHST- 2014/07/08 00:00 [accepted]
PHST- 2014/10/28 06:00 [entrez]
PHST- 2014/10/28 06:00 [pubmed]
PHST- 2015/07/22 06:00 [medline]
AID - 10.1111/acer.12512 [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2014 Oct;38(10):2597-606. doi: 10.1111/acer.12512.