长久以来，人们就意识到酒精和癌症，及癌症的扩散有着某种联系。但是这种潜在的关系是怎样的，人们对此并不知晓。而今，拉什大学医疗中心的研究学者，从细胞路径的角度，科学地解读了这一关系。
在最近发表的一篇题为“酒精中毒的临床及实验研究”的报告中称，酒精能刺激上皮细胞间的传递性，使癌症细胞变得更具有攻击性，从而扩散到人体全身各处。
拉什大学医疗中心医药及生化专业助教，即本研究的主要作者，克里斯托弗·福斯博士说，“我们的数据首次展示了酒精在细胞内部所表达出的讯息。这与细胞之间的传递性密切相关。”
目前，对于上皮细胞间的传递性的研究，是很热门的研究领域。因为在这一过程当中，癌症细胞的稳定性变弱。很多的实验室及医疗研究机构都认为，酒精能刺激癌细胞变得更具有攻击性。
福斯说，“当癌细胞发生转移的时候，它的危险性也增强了。尽管外科手术能切除肿瘤，但是具有攻击性的肿瘤细胞却能入侵到身体肌肉的各处。如果我们能阻挠癌细胞之间的传递，我们就能控制癌症扩散的速度。”
研究人员用酒精对结肠及乳腺癌细胞系进行处理，查看上皮细胞间传递时的生化特点，包括被称为“施耐勒”的转录因子，及表皮生长因子的感受器等。当用小鼠进行试验时，“施耐勒”控制着上皮细胞间的传递性，它导致了肿瘤的增生。福斯说，“癌症细胞需要大量的表皮生长因子，它们对此成瘾。”
实验室测试表明，酒精能激活上皮细胞间传递性。测试还发现，酒精处理过的细胞与邻近的细胞失去了紧密的联系，就像不稳定的细胞那样，变得更容易转移了。
此外，福斯及其同事还发现，在用酒精处理过的肠道细胞当中，同样的具有生物标记的细胞被激活，这表明，酒精不仅能使现有的癌细胞恶化，而且还能通过刺激上皮细胞间传递性，刺激癌症的发生。（生物谷Bioon.com）
生物谷推荐原始出处：
Alcoholism: Clinical and Experimental Research DOI:10.1111/j.1530-0277.2009.01061.x
Alcohol Stimulates Activation of Snail, Epidermal Growth Factor Receptor Signaling, and Biomarkers of Epithelial–Mesenchymal Transition in Colon and Breast Cancer Cells
Christopher B. Forsyth, Yueming Tang, Maliha Shaikh, Lijuan Zhang, and Ali Keshavarzian
From the Department of Internal Medicine, Section of Gastroenterology, Rush University Medical Center, Chicago, Illinois.
Background: Alcohol consumption is associated with the risk of progressive cancers including colon and breast cancer. The mechanisms for the alcohol-induced aggressive behavior of these epithelial cancer cells have not been fully identified. Epithelial–mesenchymal transition (EMT) is a developmental program recently shown to play a role in cancer progression and metastases. We hypothesized that alcohol might promote cancer progression by inducing EMT in cancer cells and tested this hypothesis by assessing alcohol-stimulated changes in phenotypic markers of EMT as well as the EMT transcription factor Snail and its related cell signaling.
Methods: Colon and breast cancer cell lines and a normal intestinal epithelial cell line were tested as well as colonic mucosal biopsy samples from alcoholic subjects. Cells were treated with alcohol and assessed for EMT-related changes using immunofluorescent microscopy, western blotting, reporter assays, RT-PCR, and knockdown of Snail with siRNA.
Results: We show alcohol upregulated the signature EMT phenotypic marker vimentin as well as matrix metalloprotease (MMP)-2, MMP-7, and MMP-9 and cell migration in colon and breast cancer cells—all characteristics of EMT. Alcohol also stimulated nuclear localization of Snail phosphorylated at Ser246, transcription from a Snail reporter plasmid, and Snail mRNA expression by RT-PCR. Snail siRNA knockdown prevented alcohol-stimulated vimentin expression. In vivo, Snail expression was significantly elevated in colonic mucosal biopsies from alcoholics. Also, we found alcohol stimulated activation of epidermal growth factor receptor (EGFR) signaling and an EGFR inhibitor blocked alcohol-induced cell migration and Snail mRNA expression.
Conclusions: Collectively, our data support a novel mechanism for alcohol promoting cancer progression through stimulating the EMT program in cancer cells via an EGFR-Snail mediated pathway. This study reveals new pathways for alcohol-mediated promotion of cancer that could be targeted for therapy or prevention of alcohol-related cancers.
