Kang Rui, Tang Daolin
Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.
J Pancreatol. 2018 Dec;1(1):19-24.
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of exocrine pancreatic cancer with a 9% five-year survival rate. High mobility group box 1 (HMGB1) is a nuclear protein that can act as a DNA chaperone in the sustainment of chromosome structure and function. When released into the extracellular space, HMGB1 becomes the most well-characterized damage-associated molecular pattern (DAMP) to trigger immune responses. Recent evidence indicates that intracellular HMGB1 is a novel tumor suppressor in PDAC, which is connected to its role in the prevention of oxidative stress, genomic instability, and histone release. However, since extracellular HMGB1 is a DAMP and pro-inflammatory cytokine, cancer cells can also exploit it to survive through the receptor for advanced glycation endproducts (RAGE) in the pancreatic tumor microenvironment. Interestingly, targeting the HMGB1-RAGE pathway has become a new anticancer therapy strategy for PDAC.
胰腺导管腺癌（PDAC）是最常见的外分泌性胰腺癌类型，五年生存率为9%。高迁移率族蛋白B1（HMGB1）是一种核蛋白，在维持染色体结构和功能方面可作为DNA伴侣蛋白。当释放到细胞外空间时，HMGB1成为最具特征的损伤相关分子模式（DAMP），以触发免疫反应。最近的证据表明，细胞内HMGB1是PDAC中的一种新型肿瘤抑制因子，这与其在预防氧化应激、基因组不稳定和组蛋白释放中的作用有关。然而，由于细胞外HMGB1是一种DAMP和促炎细胞因子，癌细胞也可以在胰腺肿瘤微环境中通过晚期糖基化终产物受体（RAGE）利用它来存活。有趣的是，靶向HMGB1-RAGE途径已成为PDAC的一种新的抗癌治疗策略。
