RRC ID 65756
Author Hata T, Kawamoto K, Eguchi H, Kamada Y, Takamatsu S, Maekawa T, Nagaoka S, Yamada D, Iwagami Y, Asaoka T, Noda T, Wada H, Gotoh K, Masamune A, Miyoshi E, Mori M, Doki Y.
Title Fatty Acid-Mediated Stromal Reprogramming of Pancreatic Stellate Cells Induces Inflammation and Fibrosis That Fuels Pancreatic Cancer.
Journal Pancreas
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.
Volume 46(10)
Pages 1259-1266
Published 2017-1-1
DOI 10.1097/MPA.0000000000000943
PMID 28991878
MeSH Adult Aged Carcinoma, Pancreatic Ductal / genetics Carcinoma, Pancreatic Ductal / metabolism Carcinoma, Pancreatic Ductal / pathology Cell Line Cell Line, Tumor Cellular Reprogramming / drug effects* Coculture Techniques Fatty Acids / pharmacology* Female Fibrosis Humans Inflammation / metabolism* Male Middle Aged Pancreas / drug effects* Pancreas / metabolism Pancreas / pathology Pancreatic Neoplasms / genetics Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology Pancreatic Stellate Cells / drug effects* Pancreatic Stellate Cells / metabolism Stromal Cells / drug effects Stromal Cells / metabolism
IF 2.92
Human and Animal Cells hPSC-1(RCB3586)