Fatty Acid–Mediated Stromal Reprogramming of Pancreatic Stellate Cells Induces Inflammation and Fibrosis That Fuels Pancreatic Cancer

Hata, Tomoki; Kikuchi, Kôichi; Eguchi, Hidetoshi; Kamada, Y.; Takamatsu, Shinji; Maekawa, Toshiro; Nagaoka, Satoshi; Yamada, Daisaku; Iwagami, Yoshifumi; Asaoka, Tadafumi; Noda, Takehiro; Wada, Hiroshi; Gotoh, Kunihito; Masamune, Atsushi; Miyoshi, Eiji; Mori, Masaki; Doki, Yuichiro

doi:10.1097/mpa.0000000000000943

Cited by 15 publications

(9 citation statements)

References 25 publications

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“…Interestingly, similar pathological changes in the pancreas were observed by autopsy of patients with pancreatic diseases, suggesting there may be many more patients with subclinical chronic pancreatitis. Furthermore, we have demonstrated fatty acid-mediated stromal reprograming of pancreatic stellate cells, leading to pancreatic inflammation and fibrosis [7]. Several studies on the association between non-alcoholic fatty pancreas disease (NAFPD) and metabolic syndrome have been performed, and ectopic fat was shown to cause various diseases such as pancreatic cancer and insulin resistance [8–10].…”

Section: Introductionmentioning

confidence: 99%

Impact of fatty pancreas and lifestyle on the development of subclinical chronic pancreatitis in healthy people undergoing a medical checkup

Fujii

Ohno

Yamada

et al. 2019

Environ Health Prev Med

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BackgroundAlthough fat accumulation in human organs is associated with a variety of diseases, there is little evidence about the effect of a fatty pancreas on the development of subclinical chronic pancreatitis over the clinical course.MethodsWe conducted a prospective cohort study from 2008 to 2014 of patients who underwent a medical checkup consultation for fat accumulated in the pancreas. Patients included in the analysis were divided into a non-fatty pancreas group (n = 9710) and fatty pancreas group (n = 223). The primary end point was the odds ratio (OR) for chronic pancreatitis associated with fatty pancreas, which was diagnosed using ultrasonography. We used a multiple logistic regression model to estimate the OR and the corresponding 95% confidence interval (CI).ResultsNinety-two people were diagnosed with chronic pancreatitis, including both presumptive and definitive diagnoses. Twelve people were diagnosed with chronic pancreatitis by ultrasonography among the 223 patients with fatty pancreas, and 80 patients among 9710 were diagnosed with non-fatty pancreas. The crude OR was 6.85 (95% CI 3.68, 12.75), and the multiple adjusted OR was 3.96 (95% CI 2.04, 7.66).ConclusionsFat accumulation in the pancreas could be a risk factor for developing subclinical chronic pancreatitis.

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Section: Introductionmentioning

confidence: 99%

Impact of fatty pancreas and lifestyle on the development of subclinical chronic pancreatitis in healthy people undergoing a medical checkup

Fujii

Ohno

Yamada

et al. 2019

Environ Health Prev Med

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“…The prominent stromal compartment characterizing PDAC was confirmed by the increment of total proteins (PRT map) and collagen (1460/1657 and 1396/1657 ratios) . Conversely, no differences were observed in the protein pattern of PNET (PRT map; PRT/TBM, 1460/1657 and 1396/1657 ratios), consistently with its known structure, rich in small vessels and poor in fibrotic stroma .…”

Section: Resultsmentioning

confidence: 99%

Investigation of human pancreatic cancer tissues by Fourier Transform Infrared Hyperspectral Imaging

Notarstefano

Conti

Pisani

et al. 2019

Journal of Biophotonics

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Fourier-transform infrared hyperspectral imaging (FTIR-HSI) provides hyperspectral images containing both morphological and chemical information. It is widely applied in the biomedical field to detect tumor lesions, even at the early stage, by identifying specific spectral biomarkers. Pancreatic neoplasms present different prognoses and are not always easily classified by conventional analyses. In this study, tissue samples with diagnosis of pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumor were analyzed by FTIR-HSI and the spectral data compared with those from healthy and dysplastic samples. Multivariate/univariate approaches were complemented to hyperspectral images, and definite spectral markers of the different lesions identified. The malignant lesions were recognizable both from healthy/dysplastic pancreatic tissues (high values of phospholipids and triglycerides with shorter, more branched and less unsaturated alkyl chains) and between each other (different amounts of total lipids, phosphates and carbohydrates). These findings highlight different metabolic pathways characterizing the different samples, well detectable by FTIR-HSI. K E Y W O R D SFourier transform infrared hyperspectral imaging, multivariate analysis, pancreatic ductal adenocarcinoma, pancreatic neuroendocrine tumors, spectral biomarkers

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“…Quiescent pancreatic stellate cells are activated by FAs, resulting in an inflammatory environment. This FA-mediated stromal reprogramming of pancreatic stellate cells induces inflammation and fibrosis in the pancreatic cancer environment 109 . HFD-induced fatty liver activates hepatic stellate cells and promotes ECM deposition, which creates a permissive prometastatic microenvironment for hepatocellular carcinoma 110 .…”

Section: Lipid Droplet Functions In Metastatic Organotropismmentioning

confidence: 99%

The dynamic behavior of lipid droplets in the pre-metastatic niche

2020

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The pre-metastatic niche is a favorable microenvironment for the colonization of metastatic tumor cells in specific distant organs. Lipid droplets (LDs, also known as lipid bodies or adiposomes) have increasingly been recognized as lipid-rich, functionally dynamic organelles within tumor cells, immune cells, and other stromal cells that are linked to diverse biological functions and human diseases. Moreover, in recent years, several studies have described the indispensable role of LDs in the development of pre-metastatic niches. This review discusses current evidence related to the biogenesis, composition, and functions of LDs related to the following characteristics of the pre-metastatic niche: immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, reprogramming. We also address the function of LDs in mediating pre-metastatic niche formation. The potential of LDs as markers and targets for novel antimetastatic therapies will be discussed.

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Fatty Acid–Mediated Stromal Reprogramming of Pancreatic Stellate Cells Induces Inflammation and Fibrosis That Fuels Pancreatic Cancer

Cited by 15 publications

References 25 publications

Impact of fatty pancreas and lifestyle on the development of subclinical chronic pancreatitis in healthy people undergoing a medical checkup

Impact of fatty pancreas and lifestyle on the development of subclinical chronic pancreatitis in healthy people undergoing a medical checkup

Investigation of human pancreatic cancer tissues by Fourier Transform Infrared Hyperspectral Imaging

The dynamic behavior of lipid droplets in the pre-metastatic niche

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