据研究人员介绍，炎症是胰腺导管腺癌（PDAC）的一个主要风险因素。当发生在胰腺炎的背景下，KRAS突变会加速小鼠模型中肿瘤的发展。
研究人员发现，在胰腺炎完全恢复后很久，一个短暂的炎症事件使胰腺上皮细胞为随后的致癌性KRAS转化提供了条件。从急性炎症恢复后，胰腺上皮细胞显示出一种持久的适应性反应，与持续的转录和表观遗传重编程有关。这种适应性使得在随后的炎症事件中能够重新激活腺泡的导管化生（ADM），从而通过快速减少酶原生产来限制组织损伤。
研究人员提出，由于KRAS的激活性突变保持了不可逆转的ADM，它们可能是有益的，并且在复发性胰腺炎的背景下处于强烈的正向选择。
附：英文原文
Title: Epithelial memory of inflammation limits tissue damage while promoting pancreatic tumorigenesis
Author: Edoardo Del Poggetto, I-Lin Ho, Chiara Balestrieri, Er-Yen Yen, Shaojun Zhang, Francesca Citron, Rutvi Shah, Denise Corti, Giuseppe R. Diaferia, Chieh-Yuan Li, Sara Loponte, Federica Carbone, Yoku Hayakawa, Giovanni Valenti, Shan Jiang, Luigi Sapio, Hong Jiang, Prasenjit Dey, Sisi Gao, Angela K. Deem, Stefan Rose-John, Wantong Yao, Haoqiang Ying, Andrew D. Rhim, Giannicola Genovese, Timothy P. Heffernan, Anirban Maitra, Timothy C. Wang, Linghua Wang, Giulio F. Draetta, Alessandro Carugo, Gioacchino Natoli, Andrea Viale
Issue&Volume: 2021-09-17
Abstract: Inflammation is a major risk factor for pancreatic ductal adenocarcinoma (PDAC). When occurring in the context of pancreatitis, KRAS mutations accelerate tumor development in mouse models. We report that long after its complete resolution, a transient inflammatory event primes pancreatic epithelial cells to subsequent transformation by oncogenic KRAS. Upon recovery from acute inflammation, pancreatic epithelial cells display an enduring adaptive response associated with sustained transcriptional and epigenetic reprogramming. Such adaptation enables the reactivation of acinar-to-ductal metaplasia (ADM) upon subsequent inflammatory events, thereby limiting tissue damage through a rapid decrease of zymogen production. We propose that because activating mutations of KRAS maintain an irreversible ADM, they may be beneficial and under strong positive selection in the context of recurrent pancreatitis.
DOI: abj0486
Source: https://www.science.org/doi/10.1126/science.abj0486