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
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.
Pancreas. 2017 Nov/Dec;46(10):1259-1266. doi: 10.1097/MPA.0000000000000943.
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.
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.
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.
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.
胰腺导管腺癌是全球最致命的疾病之一。脂肪酸（FAs）具有影响癌细胞和肿瘤环境的特性。我们在胰腺癌与胰腺星状细胞（PSC）共培养模型中评估了脂肪酸对恶性特征的影响。本研究旨在阐明体外以及临床病理分析中PSC衍生的炎症和纤维化的脂肪酸特征。
体外模型涉及人胰腺癌细胞系PANC-1和MIA PaCa-2与人PSC的共培养。对临床组织学样本进行分析，以表征接受胰体尾切除术患者样本的手术切缘特征。
胰腺癌细胞从培养基中摄取脂质。饱和脂肪酸和不饱和脂肪酸是诱导人PSC炎症反应所必需的，并且共培养显示出纤维化变化。与非癌症患者的样本相比，胰腺导管腺癌患者的临床样本在手术切缘的正常组织中具有更多的脂肪和纤维化变化。
胰腺癌标本中的炎症和纤维化水平升高，支持了体外观察结果，并表明PSC有助于胰腺癌的发生。因此，胰腺星状细胞是抑制胰腺癌基质变化的潜在治疗靶点。
