Ofejiro B Pereye1, Yuko Nakagawa1, Takashi Sato1, Ayako Fukunaka1, Shuhei Aoyama2, Yuya Nishida2, Wakana Mizutani1, Nanami Kobayashi1, Yohei Morishita3, Tetsunari Oyama4, Reika Kawabata3, Hirotaka Watada2, Hiroki Mizukami5, Akihisa Fukuda6, Yoshio Fujitani1*(1. Laboratory of Developmental Biology and Metabolism, Institute for Molecular and Cellular Regulation, Gunma University; 2. Department of Metabolism and Endocrinology, Juntendo University Graduate School of medicine; 3. Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research; 4. Department of Diagnostic Pathology, Gunma University; 5. Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine; 6. Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, *Corresponding Author)
About
We have shown that cells expressing PP (PP cells) act as a new cell of origin for pancreatic cancer. In this study, we generated mice that activate an oncogene (SV40T) in cells expressing the endocrine marker PP. Without exception, these transgenic mice developed pancreatic adenocarcinoma as early as 3-4 weeks of age. Interestingly, abnormal pancreatic duct structures were observed extending directly from the islets, which were thought to be precancerous lesions. On the other hand, mice with SV40T activation in insulin-producing cells (β-cells) developed insulinoma, an endocrine tumor, instead of pancreatic cancer. This study is considered to be an achievement that proposes a novel pathogenic pathway for pancreatic cancer, which may lead to the development of a new classification and treatment of pancreatic cancer in the future, casting a stone on the conventional hypothesis that pancreatic cancer mainly originates from pancreatic exocrine cells.
Paper information
Ofejiro B Pereye, Yuko Nakagawa, Takashi Sato, Ayako Fukunaka, Shuhei Aoyama, Yuya Nishida, Wakana Mizutani1, Nanami Kobayashi1, Yohei Morishita, Tetsunari Oyama, Reika Kawabata, Hirotaka Watada, Hiroki Mizukami, Akihisa Fukuda, Yoshio Fujitani Identification of Ppy-lineage cells as a novel origin of pancreatic ductal adenocarcinoma. J of Pathol. 2024 June 4
Online URL
https://pathsocjournals.onlinelibrary.wiley.com/doi/full/10.1002/path.6295
