@article{4a558b181cad47cd9f82ed074679ed3b,
title = "Fatty Acid-Mediated Stromal Reprogramming of Pancreatic Stellate Cells Induces Inflammation and Fibrosis That Fuels Pancreatic Cancer",
abstract = "Objectives Pancreatic ductal adenocarcinoma is one of the deadliest diseases worldwide. Fatty acids (FAs) have properties that affect both cancer cells and tumor environment. We assessed the effects of FAs on malignant characteristics in a pancreatic cancer and pancreatic stellate cell (PSC) coculture model. This study aimed to clarify the FA signature of PSC-derived inflammation and fibrosis in vitro and in a clinicopathological analysis. Methods The in vitro model involved coculture of the human pancreatic cancer cell lines PANC-1 and MIA PaCa-2 with human PSCs. Clinical histological samples were analyzed to characterize the surgical margins of samples from patients who received distal pancreatectomies. Results The pancreatic cancer cells took up lipids from the culture media. Saturated and unsaturated FAs were required to induce inflammatory responses in human PSCs, and the cocultures showed fibrotic changes. Clinical samples from pancreatic ductal adenocarcinoma patients had more fatty and fibrotic changes in the normal tissue in the surgical margins than samples from noncancer patients. Conclusions Inflammation and fibrosis levels were increased in pancreatic cancer specimens, supporting the in vitro observations and suggesting that PSCs contribute to pancreatic carcinogenesis. Pancreatic stellate cells thus represent a potential therapeutic target for suppressing stromal changes in pancreatic cancer.",
author = "Tomoki Hata and Koichi Kawamoto and Hidetoshi Eguchi and Yoshihiro Kamada and Shinji Takamatsu and Tomohiro Maekawa and Satoshi Nagaoka and Daisaku Yamada and Yoshifumi Iwagami and Tadafumi Asaoka and Takehiro Noda and Hiroshi Wada and Kunihito Gotoh and Atsushi Masamune and Eiji Miyoshi and Masaki Mori and Yuichiro Doki",
note = "Funding Information: From the Departments of *Gastroenterological Surgery, and †Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka; and ‡Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. Received for publication December 8, 2016; accepted September 8, 2017. Address correspondence to: Hidetoshi Eguchi, MD, PhD, Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565–0871 Japan (e‐mail: heguchi@gesurg.med.osaka-u.ac.jp). Eiji Miyoshi, MD, PhD, Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1–7 Yamada-oka, Suita, Osaka, 565–0871 Japan (e‐mail: emiyoshi@sahs.med.osaka-u.ac.jp). This study was partially supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology, Japan: 15H05791 to M. Mori, 25462111 to H. Eguchi, and H16K15591 to K. Kawamoto. The authors declare no conflict of interest. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal{\textquoteright}s Web site (www.pancreasjournal.com). Copyright {\textcopyright} 2017 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/MPA.0000000000000943 Publisher Copyright: {\textcopyright} 2017 Wolters Kluwer Health, Inc. All rights reserved.",
year = "2017",
month = nov,
day = "1",
doi = "10.1097/MPA.0000000000000943",
language = "English",
volume = "46",
pages = "1259--1266",
journal = "Pancreas",
issn = "0885-3177",
publisher = "Lippincott Williams and Wilkins",
number = "10",
}
