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.
| Original language | English |
|---|---|
| Pages (from-to) | 1259-1266 |
| Number of pages | 8 |
| Journal | Pancreas |
| Volume | 46 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Nov 1 2017 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Hepatology
- Endocrinology
Cite this
Fatty Acid-Mediated Stromal Reprogramming of Pancreatic Stellate Cells Induces Inflammation and Fibrosis That Fuels Pancreatic Cancer. / Hata, Tomoki; Kawamoto, Koichi; Eguchi, Hidetoshi; Kamada, Yoshihiro; Takamatsu, Shinji; Maekawa, Tomohiro; Nagaoka, Satoshi; Yamada, Daisaku; Iwagami, Yoshifumi; Asaoka, Tadafumi; Noda, Takehiro; Wada, Hiroshi; Gotoh, Kunihito; Masamune, Atsushi; Miyoshi, Eiji; Mori, Masaki; Doki, Yuichiro.
In: Pancreas, Vol. 46, No. 10, 01.11.2017, p. 1259-1266.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Fatty Acid-Mediated Stromal Reprogramming of Pancreatic Stellate Cells Induces Inflammation and Fibrosis That Fuels Pancreatic Cancer
AU - Hata, Tomoki
AU - Kawamoto, Koichi
AU - Eguchi, Hidetoshi
AU - Kamada, Yoshihiro
AU - Takamatsu, Shinji
AU - Maekawa, Tomohiro
AU - Nagaoka, Satoshi
AU - Yamada, Daisaku
AU - Iwagami, Yoshifumi
AU - Asaoka, Tadafumi
AU - Noda, Takehiro
AU - Wada, Hiroshi
AU - Gotoh, Kunihito
AU - Masamune, Atsushi
AU - Miyoshi, Eiji
AU - Mori, Masaki
AU - Doki, Yuichiro
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85032176677&partnerID=8YFLogxK
U2 - 10.1097/MPA.0000000000000943
DO - 10.1097/MPA.0000000000000943
M3 - Article
C2 - 28991878
AN - SCOPUS:85032176677
VL - 46
SP - 1259
EP - 1266
JO - Pancreas
JF - Pancreas
SN - 0885-3177
IS - 10
ER -