Levi Edi, Misra Sandhya, Du Jianhua, Patel Bhaumik B, Majumdar Adhip P N
Department of Veterans Affairs Medical Center, Wayne State University, Detroit, MI 48201, USA.
Biochem Biophys Res Commun. 2009 Jul 31;385(3):430-3. doi: 10.1016/j.bbrc.2009.05.080. Epub 2009 May 22.
Aging is associated with increased incidence of colon cancers. It is also becoming evident that cancer stem cells (CSC) play a vital role in the pathogenesis and prognosis of colon cancer. Recently, we reported the presence of colon cancer stem-like cells in macroscopically normal mucosa in patients with adenomatous polyps and that they increase with aging, suggesting that aging may predispose the colon to carcinogenesis. In the current study we have examined the combined effects of aging and carcinogen exposure on the status of colon CSCs in an experimental model. We used young (4-6 months) and aged (22-24 months) rats and exposed them to the carcinogen, dimethylhydroxide (DMH). We investigated the expression of colon cancer stem cell markers, CD44, CD166, EpCam, and ALDH1 as well as EGFR expression in normal colonic crypt epithelium following carcinogen treatment. Our results demonstrate that aging per se or carcinogen treatment alone causes an increase in the number of colon cancer stems cells, as evidenced by increased immunoreactive-CSC-markers positive cells in the colonic mucosa. In aged rats, carcinogen exposure results in a more pronounced increase in colon cancer stem cells. Our study shows that in aging colon the effects of carcinogens are more pronounced, and an increase in colon CSCs is one of the earliest changes preceding tumor development. Moreover, the current investigation of the use of a panel of immunohistochemical markers of colon CSC can potentially serve as a prognostic marker during screening for colon cancer.
衰老与结肠癌发病率的增加有关。越来越明显的是，癌症干细胞（CSC）在结肠癌的发病机制和预后中起着至关重要的作用。最近，我们报道了在患有腺瘤性息肉的患者的宏观正常黏膜中存在结肠癌干细胞样细胞，并且它们随着年龄的增长而增加，这表明衰老可能使结肠易于发生癌变。在当前的研究中，我们在一个实验模型中研究了衰老和致癌物暴露对结肠CSC状态的联合影响。我们使用了年轻（4 - 6个月）和年老（22 - 24个月）的大鼠，并将它们暴露于致癌物二甲基羟胺（DMH）。我们研究了致癌物处理后正常结肠隐窝上皮中结肠癌干细胞标志物CD44、CD166、EpCam和ALDH1的表达以及EGFR的表达。我们的结果表明，衰老本身或单独的致癌物处理都会导致结肠癌干细胞数量增加，结肠黏膜中免疫反应性CSC标志物阳性细胞的增加证明了这一点。在老年大鼠中，致癌物暴露导致结肠癌干细胞数量更明显的增加。我们的研究表明，在衰老的结肠中，致癌物的作用更明显，结肠CSC的增加是肿瘤发生之前最早的变化之一。此外，目前对一组结肠CSC免疫组化标志物的研究有可能在结肠癌筛查期间作为一种预后标志物。
