title: A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver.
abstract: Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P < 0.001), postalcohol (2.0-fold, P < 0.01), and alcohol groups (2.2-fold, P < 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P < 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFα, IL1β, IL6, and IFNγ protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8(+) T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698-704. ©2016 AACR.
authors: Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical Collage of Daejeon University, Jung-gu, Daejeon, Republic of Korea.
authors: Hwi-Jin
authors: HJ
authors: Im
authors: Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical Collage of Daejeon University, Jung-gu, Daejeon, Republic of Korea.
authors: Hyeong-Geug
authors: HG
authors: Kim
authors: Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical Collage of Daejeon University, Jung-gu, Daejeon, Republic of Korea.
authors: Jin-Seok
authors: JS
authors: Lee
authors: Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical Collage of Daejeon University, Jung-gu, Daejeon, Republic of Korea.
authors: Hyo-Seon
authors: HS
authors: Kim
authors: Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical Collage of Daejeon University, Jung-gu, Daejeon, Republic of Korea.
authors: Jung-Hyo
authors: JH
authors: Cho
authors: Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, South Korea.
authors: Il-Joo
authors: IJ
authors: Jo
authors: Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, South Korea.
authors: Sung-Joo
authors: SJ
authors: Park
authors: Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical Collage of Daejeon University, Jung-gu, Daejeon, Republic of Korea. ckson@dju.ac.kr.
authors: Chang-Gue
authors: CG
authors: Son
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects* / Q000473:pathology; D000818:Animals; D049109:Cell Proliferation; D002908:Chronic Disease; D003110:Colonic Neoplasms / Q000209:etiology* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis