Review
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Dec 6, 2018; 6(15): 882-891
Published online Dec 6, 2018. doi: 10.12998/wjcc.v6.i15.882
Inflammation and de-differentiation in pancreatic carcinogenesis
Takahiro Seimiya, Motoyuki Otsuka, Takuma Iwata, Eri Tanaka, Tatsunori Suzuki, Kazuma Sekiba, Mari Yamagami, Rei Ishibashi, Kazuhiko Koike
Takahiro Seimiya, Motoyuki Otsuka, Takuma Iwata, Eri Tanaka, Tatsunori Suzuki, Kazuma Sekiba, Mari Yamagami, Rei Ishibashi, Kazuhiko Koike, Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
Author contributions: Seimiya T and Otsuka M wrote the manuscript; Iwata T, Tanaka E, Suzuki T, Sekiba K, Yamagami M and Ishibashi R prepared the figures; Koike K supervised the entire project.
Supported by the Research Program on Hepatitis from Japan Agency for Medical Research and Development, AMED to Otsuka M, No. JP18fk0210214; and the Project for Cancer Research and Therapeutic Evolution (P-CREATE) from AMED to Otsuka M, No. JP19cm0106602.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Motoyuki Otsuka, MD, PhD, Assistant Professor, Doctor, Lecturer, Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. otsukamo-tky@umin.ac.jp
Telephone: +81-3-58008812 Fax: +81-3-38140021
Received: September 3, 2018
Peer-review started: September 3, 2018
First decision: October 11, 2018
Revised: October 26, 2018
Accepted: November 14, 2018
Article in press: November 15, 2018
Published online: December 6, 2018
Processing time: 94 Days and 10.5 Hours
Abstract

Pancreatic cancer is a malignancy with an extremely poor prognosis. Chronic pancreatitis is a well-known risk factor for pancreatic cancer. Inflammation is thought to influence carcinogenesis through DNA damage and activation of intracellular signaling pathways. Many transcription factors and signaling pathways co-operate to determine and maintain cell identity at each phase of pancreatic organogenesis and cell differentiation. Recent studies have shown that carcinogenesis is promoted through the suppression of transcription factors related to differentiation. Pancreatitis also demonstrates transcriptional changes, suggesting that multifactorial epigenetic changes lead to impaired differentiation. Taken together, these factors may constitute an important framework for pancreatic carcinogenesis. In this review, we discuss the role of inflammation and de-differentiation in the development of pancreatic cancer, as well as the future of novel therapeutic applications.

Keywords: Pancreatitis; Inflammation; Organogenesis; Differentiation; Transcription factor; Pancreatic cancer

Core tip: Inflammation is involved in carcinogenesis by causing DNA damage. Recent studies show that carcinogenesis is promoted by reprogramming factors and by suppressing transcription factors related to acinar cell differentiation. Pancreatitis also shows such transcriptional changes, suggesting that epigenetic changes by several causes leading to the impaired differentiation may constitute an important framework for pancreatic carcinogenesis. New diagnostic, preventive and/or treatment strategies based on the findings described in this review are expected to be clinically applied in the near future.