Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical Collage of Daejeon University, Jung-gu, Daejeon, Republic of Korea.
Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, South Korea.
Cancer Res. 2016 Apr 1;76(7):1698-704. doi: 10.1158/0008-5472.CAN-15-2114. Epub 2016 Feb 8.
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.
肝转移是结直肠癌死亡的主要原因。饮酒会影响肝功能，并被认为是结直肠癌肝转移的独立危险因素，但迄今为止尚无实验证据支持这一假说。在这项研究中，我们研究了饮酒对肝转移的影响。我们观察了在注射肿瘤前 4 周给予酒精（预酒精组）、注射肿瘤后 3 周给予酒精（后酒精组）或整个 7 周研究期间给予酒精（酒精组）的小鼠脾脏中结肠癌细胞的扩散情况。饮酒显著增加了预酒精组（2.4 倍，P<0.001）、后酒精组（2.0 倍，P<0.01）和酒精组（2.2 倍，P<0.001）的肝转移负荷。基于荧光的转移追踪测定也证实了酒精诱导肝内肿瘤细胞丰度增加（2.5 倍，P<0.001）。对宿主微环境的研究表明，酒精诱导的炎症反应导致 TNFα、IL1β、IL6 和 IFNγ 蛋白水平升高，以及肝组织中细胞间分子-1（ICAM1）表达增加，在酒精消耗 4 周后更为明显。此外，给予酒精 4 周的小鼠外周血中自然杀伤细胞和 CD8(+) T 细胞计数减少。总之，我们的研究结果表明，慢性饮酒通过改变肝微环境和免疫监视失活加速了结直肠癌细胞的肝转移。Cancer Res; 76(7); 1698-704. ©2016 AACR.
