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Pancreatic stellate cell

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https://www.readbyqxmd.com/read/29778400/stromal-heterogeneity-in-pancreatic-cancer-and-chronic-pancreatitis
#1
Lena Haeberle, Katja Steiger, Anna Melissa Schlitter, Sami Alexander Safi, Wolfram Trudo Knoefel, Mert Erkan, Irene Esposito
BACKGROUND/OBJECTIVES: An abundant stromal reaction is a hallmark of pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). The cells mainly responsible for the stromal reaction are activated pancreatic stellate cells (PSCs). Despite their crucial role, PSCs are not well characterized. PSCs share characteristics with the better-known hepatic stellate cells (HSCs). The aim of this study was a detailed analysis of PSCs in PDAC and CP. METHODS: Whole-slide specimens of CP (n = 12) and PDAC (n = 10) were studied by histochemistry and immunohistochemistry...
May 12, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29708625/role-of-the-wilms-tumor-suppressor-gene-wt1-in-pancreatic-development
#2
Laura Ariza, Ana Cañete, Anabel Rojas, Ramón Muñoz-Chápuli, Rita Carmona
The Wilms tumor suppressor gene (Wt1) encodes a transcription factor involved in the development of a number of organs, but the role played by Wt1 in pancreatic development is unknown. The pancreas contains a population of pancreatic stellate cells (PSC) very important for pancreatic physiology. We described elsewhere that hepatic stellate cells originate from the WT1-expressing liver mesothelium. Thus, we checked if the origin of PSCs was similar. WT1 is expressed in the pancreatic mesothelium. Between E10...
April 30, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29705706/respective-roles-of-the-mitogen-activated-protein-kinase-mapk-family-members-in-pancreatic-stellate-cell-activation-induced-by-transforming-growth-factor-%C3%AE-1-tgf-%C3%AE-1
#3
Xiao-Fan Xu, Fang Liu, Jia-Qi Xin, Jian-Wei Fan, Nan Wu, Lin-Jia Zhu, Li-Fang Duan, Yong-Yu Li, Hong Zhang
Activated pancreatic stellate cells (PSCs) play a crucial role in the progression of pancreatic fibrosis. Transforming growth factor-β (TGF-β) is one of the strongest stimulator inducing fibrosis. The mitogen-activated protein kinase (MAPK) proteins (including ERK, JNK and p38 MAPK) are known to contribute to PSC activation and pancreatic fibrosis. Previous studies have identified PSC activation induced by TGF-β1 is related to MAPK pathway, but the respective role of MAPK family members in PSC activation still unclear, and which family member may be the key mediator in mice PSC activation still controversial...
April 26, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29626466/substance-p-preserves-pancreatic-%C3%AE-cells-in-type-1-and-type-2-diabetic-mice
#4
Jihyun Um, Neunggum Jung, Dongjin Kim, Sanghyuk Choi, Sang-Ho Lee, Youngsook Son, Ki-Sook Park
Preservation of pancreatic β-cells is required for the development of therapies for type 1 and type 2 diabetes (T1D and T2D, respectively). Our previous study demonstrated that substance P (SP) preserves β-cell populations in mice with streptozotocin-induced T1D. Here, we demonstrated that chronic systemic treatment with SP restored the mass of β-cells both in nonobese diabetic (NOD) mice with T1D or db/db mice with T2D. SP delayed the onset of T1D in NOD mice via immune modulation. SP inhibited immune infiltration into islets and the salivary glands of NOD mice...
April 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29619774/pyruvate-kinase-isozyme-m2-plays-a-critical-role-in-the-interactions-between-pancreatic-stellate-cells-and-cancer-cells
#5
Atsushi Masamune, Shin Hamada, Naoki Yoshida, Tatsuhide Nabeshima, Tooru Shimosegawa
BACKGROUND: The interaction between pancreatic cancer cells and pancreatic stellate cells plays a pivotal role in the progression of pancreatic cancer. Pyruvate kinase isozyme M2 is a key enzyme in glycolysis. Previous studies have shown that pyruvate kinase isozyme M2 is overexpressed in pancreatic cancer and that it regulates the aggressive behaviors of pancreatic cancer cells. AIMS: To clarify the role of pyruvate kinase isozyme M2 in the interactions between pancreatic cancer cells and pancreatic stellate cells...
April 4, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29619382/a-transcriptional-sequencing-analysis-of-islet-stellate-cell-and-pancreatic-stellate-cell
#6
Xiaohang Wang, Wei Li, Juan Chen, Sheng Zhao, Shanhu Qiu, Han Yin, Vladmir Carvalho, Yunting Zhou, Ruifeng Shi, Jiannan Hu, Shenyi Li, Munire Nijiati, Zilin Sun
Background: Our previous studies have shown that islet stellate cell (ISC), similar to pancreatic stellate cell (PSC) in phenotype and biological characters, may be responsible for the islet fibrosis in type 2 diabetes. To further identify the differences between PSC and ISC and for better understanding of the physiological function of ISC, we employed genome-wide transcriptional analysis on the PSCs and ISCs of Wistar rats. Method: PSCs and ISCs from each rat were primarily cultured at the same condition...
2018: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29615514/targeting-galectin-1-inhibits-pancreatic-cancer-progression-by-modulating-tumor-stroma-crosstalk
#7
Carlos A Orozco, Neus Martinez-Bosch, Pedro E Guerrero, Judith Vinaixa, Tomás Dalotto-Moreno, Mar Iglesias, Mireia Moreno, Magdolna Djurec, Françoise Poirier, Hans-Joachim Gabius, Martin E Fernandez-Zapico, Rosa F Hwang, Carmen Guerra, Gabriel A Rabinovich, Pilar Navarro
Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. A more comprehensive understanding of the complexity of PDA pathobiology, and especially of the role of the tumor microenvironment in disease progression, should pave the way for therapies to improve patient response rates. In this study, we identify galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed in PDA stroma, as a major driver of pancreatic cancer progression...
April 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29595544/luteolin-ameliorates-experimental-chronic-pancreatitis-induced-by-trinitrobenzenesulfonic-acid-in-rats
#8
Qiang Yu, Jianhong Zhu, Xiaolei Sheng, Limin Xu, Kewei Hu, Guilian Chen, Wei Wu, Wei Cai, Weichang Chen, Guojian Yin
OBJECTIVES: The purpose of this study is to assess the effect and possible mechanism of luteolin on chronic pancreatitis (CP). METHODS: Trinitrobenzenesulfonic acid-induced CP was used as CP models in vivo. After the intervention of luteolin for 28 days, chronic pancreatic injury was assessed by serum hydroxyproline and pancreatic histology. α-Smooth muscle actin (α-SMA) expression was performed to detect the activation of pancreatic stellate cells (PSCs). Pancreatic stellate cells were also isolated and cultured in vitro, and the effect of luteolin on PSCs was evaluated...
March 27, 2018: Pancreas
https://www.readbyqxmd.com/read/29589070/vitamin-a-coupled-liposomes-carrying-tlr4-silencing-shrna-induce-apoptosis-of-pancreatic-stellate-cells-and-resolution-of-pancreatic-fibrosis
#9
Yuwei Zhang, Dan Yue, Liuliu Cheng, Anliang Huang, Nanwei Tong, Ping Cheng
Chronic pancreatitis leads to irreversible damage in pancreatic endocrine and exocrine functions. However, there is no clinically available antifibrotic drug. Pancreatic stellate cells (PSCs) can be activated by Toll-like receptor 4 (TLR4) responses to its ligands and they contribute to the formation of pancreatic fibrosis. Silencing the expression of TLR4 in PSCs by RNAi may be a novel therapeutic strategy for the treatment of pancreatic fibrosis. In addition, PSCs have a remarkable capacity for vitamin A uptake most likely through cellular retinol binding protein (CRBP)...
March 27, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29587800/inhibiting-yap-expression-suppresses-pancreatic-cancer-progression-by-disrupting-tumor-stromal-interactions
#10
Zhengdong Jiang, Cancan Zhou, Liang Cheng, Bin Yan, Ke Chen, Xin Chen, Liang Zong, Jianjun Lei, Wanxing Duan, Qinhong Xu, Xuqi Li, Zheng Wang, Qingyong Ma, Jiguang Ma
BACKGROUND: Hippo/YAP pathway is known to be important for development, growth and organogenesis, and dysregulation of this pathway leads to tumor progression. We and others find that YAP is up-regulated in pancreatic ductal adenocarcinoma (PDAC) and associated with worse prognosis of patients. Activated pancreatic stellate cells (PSCs) forming the components of microenvironment that enhance pancreatic cancer cells (PCs) invasiveness and malignance. However, the role and mechanism of YAP in PDAC tumor-stromal interaction is largely unknown...
March 27, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29580808/basement-membrane-destruction-by-pancreatic-stellate-cells-leads-to-local-invasion-in-pancreatic-ductal-adenocarcinoma
#11
Kazuhiro Koikawa, Kenoki Ohuchida, Yohei Ando, Shin Kibe, Hiromichi Nakayama, Shin Takesue, Sho Endo, Toshiya Abe, Takashi Okumura, Chika Iwamoto, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Takao Ohtsuka, Eishi Nagai, Kazuhiro Mizumoto, Makoto Hashizume, Masafumi Nakamura
Stroma invasion is an important step in pancreatic cancer progression. However, how pancreatic ductal adenocarcinoma (PDAC) with ductal structure invades the surrounding stroma has not been clear. Here, we elucidated the mechanism of stromal invasion of PDAC, using organoids. From resected PDAC specimens, we established human PDAC organoids, which developed ductal and basement membrane (BM) structures. When the organoids were co-cultured with pancreatic stellate cells (PSCs) in a collagen matrix, organoids lost their BM and ductal structures, and invaded collagen matrix more frequently than did mono-cultured organoids...
March 23, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29578240/necrotic-amplification-loop-in-acute-pancreatitis-pancreatic-stellate-cells-and-nitric-oxide-are-important-players-in-the-development-of-the-disease
#12
Péter Hegyi
Acute pancreatitis (AP) is a serious, life-threatening disease with high mortality. Unfortunately, there is still no specific therapy; therefore, the task remains with basic researchers. This article is protected by copyright. All rights reserved.
March 26, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29572224/il-22ra1-stat3-signaling-promotes-stemness-and-tumorigenicity-in-pancreatic-cancer
#13
Weizhi He, Jinghua Wu, Juanjuan Shi, Yan-Miao Huo, Wentao Dai, Jing Geng, Ping Lu, Min-Wei Yang, Yuan Fang, Wei Wang, Zhi-Gang Zhang, Aida Habtezion, Yong-Wei Sun, Jing Xue
Chronic inflammation is a feature of pancreatic cancer, but little is known about how immune cell or immune cell-related signal affects pancreatic cancer stemness and development. Our previous work showed that IL-22/IL-22RA1 plays a vital role in acute and chronic pancreatitis progression by mediating crosstalk between immune cells and acinar cells or stellate cells, respectively. Here we find IL-22RA1 is highly but heterogeneously expressed in pancreatic cancer cells, with high expression associated with poor prognosis of pancreatic cancer patients...
March 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29565462/indometacin-inhibits-the-proliferation-and-activation-of-human-pancreatic-stellate-cells-through-the-downregulation-of-cox-2
#14
Liankang Sun, Ke Chen, Zhengdong Jiang, Xin Chen, Jiguang Ma, Qingyong Ma, Wanxing Duan
Increasing evidence indicates that pancreatic stellate cells (PSCs) are responsible for the stromal reaction in pancreatic ductal adenocarcinoma (PDAC). The interaction between activated PSCs and PDAC cells and the resultant stromal reaction facilitate cancer progression. Previous findings suggested that cyclooxygenase‑2 (COX‑2) may have a profound role in regulating the proliferation and activation of PSCs in response to pancreatic cancer. Indometacin, a well‑known anti‑inflammatory drug and a non‑selective inhibitor of COX‑2, has been shown to exert anticancer effects in various types of cancer, including PDAC...
May 2018: Oncology Reports
https://www.readbyqxmd.com/read/29545933/endogenous-chrna7-ligand-slurp1-as-a-potential-tumor-suppressor-and-anti-nicotinic-factor-in-pancreatic-cancer
#15
Verena M Throm, David Männle, Thomas Giese, Andrea S Bauer, Matthias M Gaida, Juergen Kopitz, Thomas Bruckner, Konstanze Plaschke, Svetlana P Grekova, Klaus Felix, Thilo Hackert, Nathalia A Giese, Oliver Strobel
Smoking is associated with increased risk and poorer prognosis of pancreatic ductal adenocarcinoma (PDAC). Nicotine acts through cholinergic nicotinic receptors, preferentially α7 (CHRNA7) that also binds the endogenous ligand SLURP1 (Secreted Ly-6/uPAR-Related Protein 1). The clinical significance of SLURP1 and its interaction with nicotine in PDAC are unclear. We detected similar levels of SLURP1 in sera from healthy donors and patients with chronic pancreatitis or PDAC; higher preoperative values were associated with significantly better survival in patients with resected tumors...
February 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29490942/zeb1-in-stromal-myofibroblasts-promotes-kras-driven-development-of-pancreatic-cancer
#16
Irene Sangrador, Xavier Molero, Fiona Campbell, Sebastià Franch-Expósito, Maria Rovira-Rigau, Esther Samper, Manuel Domínguez-Fraile, Cristina Fillat, Antoni Castells, Eva C Vaquero
The transcription factor Zeb1 has been identified as a crucial player in Kras-dependent oncogenesis. In pancreatic ductal adenocarcinoma (PDAC), Zeb1 is highly expressed in myofibroblasts and correlates with poor prognosis. As Kras mutations are key drivers in PDAC, we aimed here to assess the necessity of Zeb1 for Kras-driven PDAC and to define the role of Zeb1-expressing myofibroblasts in PDAC development. Genetically engineered mice with conditional pancreatic Kras G12D and Trp53 mutations (KPC) were crossed with Zeb1 haploinsufficient mice (Z+/- )...
February 28, 2018: Cancer Research
https://www.readbyqxmd.com/read/29472102/modeling-human-pancreatic-beta-cell-dedifferentiation
#17
Marc Diedisheim, Masaya Oshima, Olivier Albagli, Charlotte Wennberg Huldt, Ingela Ahlstedt, Maryam Clausen, Suraj Menon, Alexander Aivazidis, Anne-Christine Andreasson, William G Haynes, Piero Marchetti, Lorella Marselli, Mathieu Armanet, Fabrice Chimienti, Raphael Scharfmann
OBJECTIVE: Dedifferentiation could explain reduced functional pancreatic β-cell mass in type 2 diabetes (T2D). METHODS: Here we model human β-cell dedifferentiation using growth factor stimulation in the human β-cell line, EndoC-βH1, and human pancreatic islets. RESULTS: Fibroblast growth factor 2 (FGF2) treatment reduced expression of β-cell markers, (INS, MAFB, SLC2A2, SLC30A8, and GCK) and activated ectopic expression of MYC, HES1, SOX9, and NEUROG3...
April 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29458370/the-critical-roles-of-activated-stellate-cells-mediated-paracrine-signaling-metabolism-and-onco-immunology-in-pancreatic-ductal-adenocarcinoma
#18
REVIEW
Yaojie Fu, Shanshan Liu, Shan Zeng, Hong Shen
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant diseases worldwide. It is refractory to conventional treatments, and consequently has a documented 5-year survival rate as low as 7%. Increasing evidence indicates that activated pancreatic stellate cells (PSCs), one of the stromal components in tumor microenvironment (TME), play a crucial part in the desmoplasia, carcinogenesis, aggressiveness, metastasis associated with PDAC. Despite the current understanding of PSCs as a "partner in crime" to PDAC, detailed regulatory roles of PSCs and related microenvironment remain obscure...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29435115/fibrosis-related-mirnas-as-serum-biomarkers-for-pancreatic-ductal-adenocarcinoma
#19
Rei Suzuki, Hiroyuki Asama, Yuichi Waragai, Tadayuki Takagi, Takuto Hikichi, Mitsuru Sugimoto, Naoki Konno, Ko Watanabe, Jun Nakamura, Hitomi Kikuchi, Yuki Sato, Shigeru Marubashi, Atsushi Masamune, Hiromasa Ohira
We investigated whether serum microRNAs (miRNAs) could be diagnostic or prognostic markers in pancreatic ductal adenocarcinoma (PDAC). We first identified miRNAs showing altered expression in human pancreatic stellate cells (hPSCs) co-cultured with PDAC cells (Panc-1 and BxPC-3) as compared to hPSCs cultured alone. Among the miRNAs with altered expression, let-7d exhibited reduced expression in an in silico analysis of The Cancer Genome Atlas data. Inhibition of let-7d resulted in enhanced expression of fibrosis-related genes...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29424931/calcium-signalling-in-the-acinar-environment-of-the-exocrine-pancreas-physiology-and-pathophysiology
#20
Oleksiy Gryshchenko, Julia V Gerasimenko, Shuang Peng, Oleg V Gerasimenko, Ole H Petersen
KEY POINTS: Ca2+ signalling in different cell types in exocrine pancreatic lobules was monitored simultaneously and signalling responses to various stimuli were directly compared. Ca2+ signals evoked by K+ -induced depolarization were recorded from pancreatic nerve cells. Nerve cell stimulation evoked Ca2+ signals in acinar but not in stellate cells. Stellate cells are not electrically excitable as they, like acinar cells, did not generate Ca2+ signals in response to membrane depolarization...
February 9, 2018: Journal of Physiology
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