長久以來,，人們就意識到酒精和癌癥，及癌癥的擴散有著某種聯(lián)系,。但是這種潛在的關(guān)系是怎樣的,，人們對此并不知曉。而今,，拉什大學(xué)醫(yī)療中心的研究學(xué)者，從細(xì)胞路徑的角度，科學(xué)地解讀了這一關(guān)系,。
在最近發(fā)表的一篇題為“酒精中毒的臨床及實驗研究”的報告中稱,，酒精能刺激上皮細(xì)胞間的傳遞性,，使癌癥細(xì)胞變得更具有攻擊性，從而擴散到人體全身各處,。
拉什大學(xué)醫(yī)療中心醫(yī)藥及生化專業(yè)助教,，即本研究的主要作者，克里斯托弗·福斯博士說,，“我們的數(shù)據(jù)首次展示了酒精在細(xì)胞內(nèi)部所表達(dá)出的訊息,。這與細(xì)胞之間的傳遞性密切相關(guān)。”
目前,，對于上皮細(xì)胞間的傳遞性的研究，是很熱門的研究領(lǐng)域,。因為在這一過程當(dāng)中,，癌癥細(xì)胞的穩(wěn)定性變?nèi)?。很多的實驗室及醫(yī)療研究機構(gòu)都認(rèn)為,，酒精能刺激癌細(xì)胞變得更具有攻擊性。
福斯說,，“當(dāng)癌細(xì)胞發(fā)生轉(zhuǎn)移的時候,，它的危險性也增強了,。盡管外科手術(shù)能切除腫瘤，但是具有攻擊性的腫瘤細(xì)胞卻能入侵到身體肌肉的各處,。如果我們能阻撓癌細(xì)胞之間的傳遞,，我們就能控制癌癥擴散的速度。”
研究人員用酒精對結(jié)腸及乳腺癌細(xì)胞系進(jìn)行處理,，查看上皮細(xì)胞間傳遞時的生化特點,，包括被稱為“施耐勒”的轉(zhuǎn)錄因子，及表皮生長因子的感受器等,。當(dāng)用小鼠進(jìn)行試驗時，“施耐勒”控制著上皮細(xì)胞間的傳遞性,，它導(dǎo)致了腫瘤的增生。福斯說，“癌癥細(xì)胞需要大量的表皮生長因子,，它們對此成癮,。”
實驗室測試表明，酒精能激活上皮細(xì)胞間傳遞性,。測試還發(fā)現(xiàn),，酒精處理過的細(xì)胞與鄰近的細(xì)胞失去了緊密的聯(lián)系，就像不穩(wěn)定的細(xì)胞那樣,，變得更容易轉(zhuǎn)移了,。
此外，福斯及其同事還發(fā)現(xiàn),，在用酒精處理過的腸道細(xì)胞當(dāng)中,，同樣的具有生物標(biāo)記的細(xì)胞被激活，這表明,，酒精不僅能使現(xiàn)有的癌細(xì)胞惡化,，而且還能通過刺激上皮細(xì)胞間傳遞性，刺激癌癥的發(fā)生,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
