首页 / 院系成果 / 成果详情页

ENPP1-Regulated Extracellular Purine Metabolism Drives Pancreatitis-Mediated Pancreatic Cancer 期刊论文

编号：

53EB9E0E12A560AE02890E7F10612B81
作者：

Ma, Zhilong#^[1,2,3,4,5]Dong, Mingwei^[1,2,3,4,5];Pan, Haoqi^[1,2,3,4,5];Xu, Junyi^[1,2,3,4,5];Luo, Tingyi^[6];Xie, Wangcheng^[6];Xiao, Mingming^[1,2,3,4,5];Wen, Xin^[7];Hua, Jie^[1,2,3,4,5];Qian, Daohai(钱道海)^[8]Meng, Qingcai^[1,2,3,4,5];Wang, Yufeng^[1,2,3,4,5];Wu, Di^[1,2,3,4,5];Zhang, Xiaobing^[9];Yang, Tingsong^[6];Song, Zhenshun^[10];Wang, Wei^[1,2,3,4,5];Xu, Jin^[1,2,3,4,5];Yu, Xianjun*^[1,2,3,4,5]Shi, Si*^[1,2,3,4,5]
语种：

英文
期刊：

GASTROENTEROLOGY ISSN：0016-5085 2026 年 170 卷 4 期 (735 - 752) ; APR
收录：
关键词：

Pancreatic Cancer Pancreatitis Extracellular Purine Metabolism ENPP1
摘要：

BACKGROUND & AIMS: Patients with chronic pancreatitis (CP) have a higher risk of developing pancreatic ductal adenocarcinoma (PDAC). Although pancreatitis has been found to promote PDAC initiation and progression, its role in PDAC tumorigenesis remains poorly understood. METHODS: A multiomics analysis of the transcriptome, proteome, and metabolome was performed in human pancreatic samples from patients with CP and CP-related PDAC (CP-PDAC). The CP-PDAC model was constructed in Ptf1aCre/+; LSL-KrasG12D/+ mice and Ptf1aCre/+; LSL-KrasG12D/+; ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) mice. Single-cell sequencing analysis of pancreatic tissue samples from Ptf1aCre/+; LSL-KrasG12D/+ mice and Ptf1aCre/+; LSL-KrasG12D/+; Enpp1 mice revealed the role of the immune micro-environment in the progression from pancreatitis to cancer. Pharmacologic ENPP1 inhibition was studied in the orthotopic transplantation model and CP-PDAC model mice. RESULTS: Multiomics analysis of samples from patients with CP and CP-PDAC revealed that ENPP1-regulated extracellular purine metabolism plays an important role in pancreatitis-cancer transformation. Mechanistically, inflammatory damage to pancreatic acinar cells leads to the release of purine nucleotide metabolites, which are degraded by ENPP1-CD73 on the surface of pancreatic stellate cells into adenosine. This process activates pancreatic stellate cells and promotes fibrosis. Activated pancreatic stellate cells then release CXCL17, which recruits myeloid-derived suppressor cells and regulatory T cells in the microenvironment, resulting in immunosuppressive effects. Finally, ENPP1 was confirmed to be an effective target for immunotherapy in PDAC and early intervention in pancreatitis-cancer transformation. CONCLUSIONS: The study results identified ENPP1 as a contributor to pancreatitis-mediated pancreatic cancer and a potential therapeutic target for pancreatic carcinogenesis.
推荐引用方式
GB/T 7714：

Ma Zhilong,Dong Mingwei,Pan Haoqi, et al. ENPP1-Regulated Extracellular Purine Metabolism Drives Pancreatitis-Mediated Pancreatic Cancer [J].GASTROENTEROLOGY,2026,170(4):735-752.
APA：

Ma Zhilong,Dong Mingwei,Pan Haoqi,Xu Junyi,&Shi Si.(2026).ENPP1-Regulated Extracellular Purine Metabolism Drives Pancreatitis-Mediated Pancreatic Cancer .GASTROENTEROLOGY,170(4):735-752.
MLA：

Ma Zhilong, et al. "ENPP1-Regulated Extracellular Purine Metabolism Drives Pancreatitis-Mediated Pancreatic Cancer" .GASTROENTEROLOGY 170,4(2026):735-752.
入库时间：

4/7/2026 9:51:42 PM
更新时间：

4/7/2026 9:51:42 PM

浏览次数：3  下载次数：0

分享到：

浏览次数：3

下载次数：0

打印次数：0