Alcohol consumption suppresses mammary tumor metastasis in a syngeneic tumor transplantation model
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Epidemiological studies indicate a positive correlation between alcohol consumption and the risk of developing breast cancer. However, little is known about whether alcohol consumption affects breast cancer metastasis. Considering that the primary cause of death in breast cancer patients is due to metastasis, further insight into whether alcohol consumption influences disease progression and survival is needed. We tested the effect of alcohol consumption on breast cancer metastasis using the 4T1.2 syngeneic mammary tumor model in Balb/c mice. The treatment groups included a High-consuming group (18 % w/v alcohol in drinking water), a Moderate-consuming group (5 % w/v), a Low-consuming group (1 % w/v), and a Water-drinking control group. 4T1.2 mammary tumor cells were injected orthotopically into the mammary fat pad. Metastases were enumerated in lungs and in distant mammary glands 4 weeks after injection. Consumption of High alcohol protected against metastasis, as High-consuming mice typically had 65–75 % fewer metastases compared to Water-drinking controls. A suggestive reduction in tumor spread was observed in the Moderate-drinking group, although the effects did not reach statistical significance. Consumption of the Low alcohol dose did not affect metastasis. CXCR4 expression in the primary tumors was significantly reduced by High alcohol consumption; however, expression of this chemokine receptor in the primary tumor did not correlate with metastatic potential. Additional studies were conducted to test for possible direct effects of 0.3 % w/v ethanol on tumor cell proliferation, migration, invasion, and colony formation of 4T1.2 cells in vitro. Our results indicate that, for this murine model, alcohol consumption does not exacerbate tumor metastasis, and that High alcohol consumption reduces tumor spread.
KeywordsBreast cancer Metastasis Ethanol Alcohol CXCR4 Mice
The authors would like to thank Elizabeth Wright, Hiep Nguyen, Pat Ager, and Faya Zhang for technical contributions to these experiments, and Dr. Jan Dasgupta (WSU Mathematics Department) for assistance with statistical analyses. These studies were supported by the NIH/NIAAA, including K05AA017149 to GGM with funding to BAV, R01AA07293 to GGM with a supplement to GGM and BAV, and by a grant in support of breast cancer research from the Fraternal Order of Eagles.
Conflict of interest
The authors declare that they have no conflict of interest.
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