Abstract
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.
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References
ACS (2011) American Cancer Society. Breast cancer facts and figures 2011–2012. American Cancer Society, Atlanta
Li CI, Chlebowski RT, Freiberg M, Johnson KC, Kuller L, Lane D, Lessin L, O’Sullivan MJ, Wactawski-Wende J, Yasmeen S, Prentice R (2010) Alcohol consumption and risk of postmenopausal breast cancer by subtype: the women’s health initiative observational study. J Natl Cancer Inst 102:1422–1431
Pelucchi C, Tramacere I, Boffetta P, Negri E, La Vecchia C (2011) Alcohol consumption and cancer risk. Nutr Cancer 63:983–990
AICR (2007) World Cancer Research Fund/American Institute for Cancer Research. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. American Institute for Cancer Research, Washington DC
Li Y, Yang H, Cao J (2011) Association between alcohol consumption and cancers in the Chinese population—a systematic review and meta-analysis. PLoS ONE 6:e18776
Chen WY, Rosner B, Hankinson SE, Colditz GA, Willett WC (2011) Moderate alcohol consumption during adult life, drinking patterns, and breast cancer risk. JAMA 306:1884–1890
Kwan ML, Kushi LH, Weltzien E, Tam EK, Castillo A, Sweeney C, Caan BJ (2010) Alcohol consumption and breast cancer recurrence and survival among women with early-stage breast cancer: the life after cancer epidemiology study. J Clin Oncol 28:4410–4416
Harris HR, Bergkvist L, Wolk A (2012) Alcohol intake and mortality among women with invasive breast cancer. Br J Cancer 106:592–595
Flatt SW, Thomson CA, Gold EB, Natarajan L, Rock CL, Al-Delaimy WK, Patterson RE, Saquib N, Caan BJ, Pierce JP (2010) Low to moderate alcohol intake is not associated with increased mortality after breast cancer. Cancer Epidemiol Biomark Prev 19:681–688
Beasley JM, Newcomb PA, Trentham-Dietz A, Hampton JM, Bersch AJ, Passarelli MN, Holick CN, Titus-Ernstoff L, Egan KM, Holmes MD, Willett WC (2011) Post-diagnosis dietary factors and survival after invasive breast cancer. Breast Cancer Res Treat 128:229–236
Lelekakis M, Moseley JM, Martin TJ, Hards D, Williams E, Ho P, Lowen D, Javni J, Miller FR, Slavin J, Anderson RL (1999) A novel orthotopic model of breast cancer metastasis to bone. Clin Exp Metastasis 17:163–170
Pulaski BA, Ostrand-Rosenberg S (2000) Mouse 4T1 breast tumor model. In: Coligan JE, Bierer BE, Margulies DH, Shevach EM, Strober W, Coico R (eds) Curr Protoc Immunol 20.22.21–20.22.16
Olkhanud PB, Baatar D, Bodogai M, Hakim F, Gress R, Anderson RL, Deng J, Xu M, Briest S, Biragyn A (2009) Breast cancer lung metastasis requires expression of chemokine receptor CCR4 and regulatory T cells. Cancer Res 69:5996–6004
Wang T, Wyrick KL, Meadows GG, Wills TB, Vorderstrasse BA (2011) Activation of the aryl hydrocarbon receptor by TCDD inhibits mammary tumor metastasis in a syngeneic mouse model of breast cancer. Toxicol Sci 124:291–298
Wang T, Gavin HM, Arlt VM, Lawrence BP, Fenton SE, Medina D, Vorderstrasse BA (2011) Aryl hydrocarbon receptor activation during pregnancy, and in adult nulliparous mice, delays the subsequent development of DMBA-induced mammary tumors. Int J Cancer 128:1509–1523
duPre SA, Hunter KW Jr (2007) Murine mammary carcinoma 4T1 induces a leukemoid reaction with splenomegaly: association with tumor-derived growth factors. Exp Mol Pathol 82:12–24
Williams SA, Harata-Lee Y, Comerford I, Anderson RL, Smyth MJ, McColl SR (2010) Multiple functions of CXCL12 in a syngeneic model of breast cancer. Mol Cancer 9:250
Kang H, Watkins G, Douglas-Jones A, Mansel RE, Jiang WG (2005) The elevated level of CXCR4 is correlated with nodal metastasis of human breast cancer. Breast 14:360–367
Liu J, Liao S, Huang Y, Samuel R, Shi T, Naxerova K, Huang P, Kamoun W, Jain RK, Fukumura D, Xu L (2011) PDGF-D improves drug delivery and efficacy via vascular normalization, but promotes lymphatic metastasis by activating CXCR4 in breast cancer. Clin Cancer Res 17:3638–3648
Smith MC, Luker KE, Garbow JR, Prior JL, Jackson E, Piwnica-Worms D, Luker GD (2004) CXCR4 regulates growth of both primary and metastatic breast cancer. Cancer Res 64:8604–8612
Wang S, Xu M, Li F, Wang X, Bower KA, Frank JA, Lu Y, Chen G, Zhang Z, Ke Z, Shi X, Luo J (2011) Ethanol promotes mammary tumor growth and angiogenesis: the involvement of chemoattractant factor MCP-1. Breast Cancer Res Treat 133(3):1037–1048
Wu WJ, Pruett SB (1999) Ethanol decreases host resistance to pulmonary metastases in a mouse model: role of natural killer cells and the ethanol-induced stress response. Int J Cancer 82:886–892
Meadows GG, Elstad CA, Blank SE, Gallucci RM, Pfister LJ (1993) Alcohol consumption suppresses metastasis of B16-BL6 melanoma in mice. Clin Exp Metastasis 11:191–199
Yirmiya R, Ben-Eliyahu S, Gale RP, Shavit Y, Liebeskind JC, Taylor AN (1992) Ethanol increases tumor progression in rats: possible involvement of natural killer cells. Brain Behav Immun 6:74–86
Acknowledgments
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.
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The authors declare that they have no conflict of interest.
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Vorderstrasse, B.A., Wang, T., Myers, A.K. et al. Alcohol consumption suppresses mammary tumor metastasis in a syngeneic tumor transplantation model. Breast Cancer Res Treat 136, 729–737 (2012). https://doi.org/10.1007/s10549-012-2275-2
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DOI: https://doi.org/10.1007/s10549-012-2275-2