Our Goal is to identify how colorectal cancer (CRC) arises in the single-layered cell epithelium (simple columnar epithelium) that lines the luminal surface of the large intestine.Background:We recently reported that the dynamic organization of cells in colonic epithelium is encoded by five biological rules and conjectured that colon tumorigenesis involves an autocatalytic tissue renewal reaction. Introduction Our objective was to define how altered crypt turnover explains tissue disorganization that leads to adenoma morphogenesis and CRC.Hypothesis: Changes in rate of tissue renewal-based cell polymerization leads to epithelial expansion and tissue disorganization during adenoma histogenesis.Methods:Accordingly, we created a computational model that considers the structure of colonic epithelium to be a polymer of cells and that tissue renewal is autocatalytic. Indeed, self-renewal of stem cells in colonic crypts continuously produces cells that act like monomers to form a polymer of cells (an interconnected, continuous cell sheet) in a polymerization-based process. Our model is a system of nonlinear differential equations that simulates changes in human crypt cell population dynamics.Results:We investigated how changes occur in the proportion of different cell types during adenoma development in FAP patients. The results show premalignant colonic crypts have a decreased rate of tissue renewal due toAPC-mutation.Discussion:This slower rate of cell polymerization causes a rate-limiting step in the crypt renewal process that expands the proliferative cell population size.Conclusions:Our findings provide a mechanism that explains how a prolonged rate of crypt renewal leads to tissue disorganization with local epithelial expansion, infolding, and contortion during adenoma morphogenesis.:
我们的目标是明确结直肠癌（CRC）如何起源于大肠管腔表面的单层细胞上皮（单层柱状上皮）。背景：我们近期报道了结肠上皮细胞动态组织受五条生物学规则调控，并推测结肠肿瘤发生涉及一种自催化组织更新反应。引言：我们的目的是阐明隐窝更新速率的改变如何解释导致腺瘤形态发生和结直肠癌的组织结构紊乱。假设：基于组织更新的细胞聚合速率变化导致腺瘤组织发生过程中的上皮扩张和组织结构紊乱。方法：据此，我们构建了一个计算模型，将结肠上皮结构视为细胞聚合物，并认为组织更新具有自催化特性。事实上，结肠隐窝中干细胞的自我更新持续产生细胞，这些细胞在基于聚合的过程中像单体一样形成细胞聚合物（相互连接的连续细胞层）。我们的模型是一个非线性微分方程组，用于模拟人类隐窝细胞群体动态变化。结果：我们研究了FAP患者腺瘤发展过程中不同细胞类型比例的变化。结果显示，由于APC基因突变，癌前结肠隐窝的组织更新速率降低。讨论：这种较慢的细胞聚合速率在隐窝更新过程中形成限速步骤，从而扩大了增殖细胞群体规模。结论：我们的发现提供了一个机制，解释了隐窝更新速率延长如何导致腺瘤形态发生过程中的组织结构紊乱，伴随局部上皮扩张、内陷和扭曲。
肿瘤(癌症)患者之家