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Pancreatic stellate cell

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https://www.readbyqxmd.com/read/28336327/galectin-1-driven-upregulation-of-sdf-1-in-pancreatic-stellate-cells-promotes-pancreatic-cancer-metastasis
#1
Dong Qian, Zipeng Lu, Qingcheng Xu, Pengfei Wu, Lei Tian, Liangtao Zhao, Baobao Cai, Jie Yin, Yang Wu, Kevin F Staveley-O'Carroll, Kuirong Jiang, Yi Miao, Guangfu Li
Galectin-1, mainly expressed in activated pancreatic stellate cells (PSCs), is involved in many important cancer-related processes. However, very little is known how Galectin-1 modulates PSCs and subsequently impacts pancreatic cancer cells (PCCs). Our chemokine antibody array and in vitro studies demonstrates that Galectin-1 induces secretion of stromal cell-derived factor-1(SDF-1) in PSCs by activating NF-κB signaling. The secreted SDF-1 increases migration and invasion of PCCs. Knockdown of Galectin-1 and inhibitor-mediated blockade of SDF-1 as well as its ligand CXCR4 and NF-κB verifies the findings...
March 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28322389/alteration-of-pancreatic-carcinoma-and-promyeloblastic-cell-adhesion-in-liver-microvasculature-by-co-culture-of-hepatocytes-hepatic-stellate-cells-and-endothelial-cells-in-a-physiologically-relevant-model
#2
Mathieu Danoy, Marie Shinohara, Astia Rizki-Safitri, Dominique Collard, Vincent Senez, Yasuyuki Sakai
In vitro models of the liver microvasculature, especially with respect to cancer cell extravasation, should include not only endothelial and cancer cells but also surrounding cells to mimic the physiological situation. To this end, in the present study, we established a physiologically-relevant hierarchical co-culture model by stacking layers of primary rat hepatocytes (Hep), hepatic stellate cells embedded in collagen gel (LX-2) and endothelial cells (HUVECs) on a specially designed oxygen-permeable polydimethylsiloxane PDMS bottom plate...
March 21, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28281184/tgf-%C3%AE-1-mir-200a-pten-induces-epithelial-mesenchymal-transition-and-fibrosis-of-pancreatic-stellate-cells
#3
Min Xu, Guoying Wang, Hailang Zhou, Jing Cai, Ping Li, Meng Zhou, Ying Lu, Xiaomeng Jiang, Hongmei Huang, Youli Zhang, Aihua Gong
Although the function of miR-200a has been discussed in many cancers and fibrotic diseases, its role in pancreatic fibrosis is still poorly understood. In this study, we for the first time confirm that miR-200a attenuates TGF-β1-induced pancreatic stellate cells activation and extracellular matrix formation. First, we find that TGF-β1 induces activation and extracellular matrix (ECM) formation in PSCs, and the effects are blocked by the inhibitor of PI3K (LY294002). Furthermore, we identify that miR-200a is down-regulated in TGF-β1-activated PSCs, and up-regulation of miR-200a inhibits PSCs activation induced by TGF-β1...
March 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28276831/pancreatic-cancer-stroma-controversies-and-current-insights
#4
Daniel Ansari, Maria Carvajo, Monika Bauden, Roland Andersson
Pancreatic cancer is characterized by a dense stromal response. The stroma includes a heterogeneous mass of cells, including pancreatic stellate cells, fibroblasts, immune cells and nerve cells, as well as extracellular matrix proteins, cytokines and growth factors, which interact with the tumor cells. Previous research has indicated that stromal elements contribute to tumor growth and aggressiveness. However, recent studies suggest that some elements of the stroma may actually restrain the tumor. This review focuses on the complex interactions between the stromal microenvironment and tumor cells, discussing molecular mechanisms and potential future diagnostic and therapeutic approaches by targeting the stroma...
February 24, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28249896/lipocalin-2-promotes-pancreatic-ductal-adenocarcinoma-by-regulating-inflammation-in-the-tumor-microenvironment
#5
Sobeyda Gomez-Chou, Agnieszka Swidnicka-Siergiejko, Niharika Badi, Myrriah Chavez-Tomar, Gregory B Lesinski, Tanios Bekaii-Saab, Matthew R Farren, Thomas A Mace, Carl Schmidt, Yan Liu, Defeng Deng, Rosa F Hwang, Liran Zhou, Todd T Moore, Deyali Chatterjee, Huamin Wang, Xiaohong Leng, Ralph B Arlinghaus, Craig D Logsdon, Zobeida Cruz-Monserrate
Lipocalin-2 (LCN2) promotes malignant development in many cancer types. LCN2 is upregulated in patients with pancreatic ductal adenocarcinoma (PDAC) and in obese individuals, but whether it contributes to PDAC development is unclear. In this study, we investigated the effects of Lcn2 depletion on diet-induced obesity, inflammation and PDAC development. Mice with acinar cell-specific expression of KrasG12D were crossed with Lcn2-depleted animals and fed isocaloric diets with varying amounts of fat content. Pancreas were collected and analyzed for inflammation, pancreatic intraepithelial neoplasia (PanIN) and PDAC...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28217371/pathogenic-mechanisms-of-pancreatitis
#6
REVIEW
Murli Manohar, Alok Kumar Verma, Sathisha Upparahalli Venkateshaiah, Nathan L Sanders, Anil Mishra
Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28210075/pancreatic-stellate-cell-pandora-s-box-for-pancreatic-disease-biology
#7
REVIEW
Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar
Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin...
January 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28202235/stx12-lncrna-mir-148a-smad5-participate-in-the-regulation-of-pancreatic-stellate-cell-activation-through-a-mechanism-involving-competing-endogenous-rna
#8
Hao Wang, Yanfeng Jiang, Ming Lu, Bei Sun, Xin Qiao, Dongbo Xue, Weihui Zhang
BACKGROUND: With the deepening of research, the roles of LncRNAs play in the fibrotic process have attracted great attention. At the early stage of pancreatic fibrogenesis, to effectively regulate pancreatic stellate cells (PSCs) activation is crucial for the treatment of chronic pancreatic fibrosis. METHODS: Microarray data on chronic pancreatitis were retrieved from the Gene Expression Omnibus (GEO) repository and analyzed using bioinformatic methods. A diagram of the lncRNA-miRNA-mRNA ceRNA network was constructed...
February 1, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28196027/mk2461-a-multitargeted-kinase-inhibitor-suppresses-the-progression-of-pancreatic-cancer-by-disrupting-the-interaction-between-pancreatic-cancer-cells-and-stellate-cells
#9
Koetsu Inoue, Hideo Ohtsuka, Masanori Tachikawa, Fuyuhiko Motoi, Masahiro Shijo, Daisuke Douchi, Shuhei Kawasaki, Kei Kawaguchi, Kunihiro Masuda, Koji Fukase, Takeshi Naitoh, Yu Katayose, Shinichi Egawa, Michiaki Unno, Tetsuya Terasaki
OBJECTIVES: Platelet-derived growth factor receptor beta (PDGFRβ) and hepatocyte growth factor receptor (MET) expressed on pancreatic stellate cells (PSCs) are suggested as important components modulating the interactions between pancreatic cancer cells (PCCs) and PSCs. The objective of this study is to clarify the effect of MK2461, a multikinase inhibitor targeting MET and PDGFRβ, on the interaction between PCCs and PSCs. METHODS: In this study, we profiled the expression of receptor tyrosine kinases (including PDGFRβ and MET) in pancreatic cancer with quantitative targeted absolute proteomics using liquid chromatography tandem mass spectrometry...
April 2017: Pancreas
https://www.readbyqxmd.com/read/28194432/bet-inhibitors-block-pancreatic-stellate-cell-collagen-i-production-and-attenuate-fibrosis-in-vivo
#10
Krishan Kumar, Brian T DeCant, Paul J Grippo, Rosa F Hwang, David J Bentrem, Kazumi Ebine, Hidayatullah G Munshi
The fibrotic reaction, which can account for over 70%-80% of the tumor mass, is a characteristic feature of human pancreatic ductal adenocarcinoma (PDAC) tumors. It is associated with activation and proliferation of pancreatic stellate cells (PSCs), which are key regulators of collagen I production and fibrosis in vivo. In this report, we show that members of the bromodomain and extraterminal (BET) family of proteins are expressed in primary PSCs isolated from human PDAC tumors, with BRD4 positively regulating, and BRD2 and BRD3 negatively regulating, collagen I expression in primary cancer-associated PSCs...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28182873/biomechanically-primed-liver-microtumor-array-as-a-high-throughput-mechanopharmacological-screening-platform-for-stroma-reprogrammed-combinatorial-therapy
#11
Lu Zhu, Xingliang Fan, Bingjie Wang, Longwei Liu, Xiaojun Yan, Lyu Zhou, Yang Zeng, Mark C Poznansky, Lili Wang, Huabiao Chen, Yanan Du
Recent breakthrough in stroma-reprogrammed combinatorial therapy (SRCT) for pancreatic tumor opens a new route for improving conventional chemotherapeutic efficacy, which utilizes VDR ligand to reprogram activated stromal cells in stiffened microenvironment, leading to reduced 'barrier effects' and increased tissue-infiltration of the chemotherapy drug. As a novel therapeutic strategy and mechanism of action, the progress of SRCT relies on tailored in vitro drug assessment platforms to further optimize its efficacy and extend to applications in other tumor types...
January 27, 2017: Biomaterials
https://www.readbyqxmd.com/read/28174730/inhibitors-of-arg-gly-asp-binding-integrins-reduce-development-of-pancreatic-fibrosis-in-mice
#12
Barbara Ulmasov, Brent A Neuschwander-Tetri, Jinping Lai, Vladimir Monastyrskiy, Trisha Bhat, Matthew P Yates, Jonathan Oliva, Michael J Prinsen, Peter G Ruminski, David W Griggs
BACKGROUND & AIMS: Pancreatic stellate cells (PSCs) regulate the development of chronic pancreatitis (CP) and are activated by the cytokine transforming growth factor β (TGFB). Integrins of the αv family promote TGFB signaling in mice, probably by interacting with the Arg-Gly-Asp (RGD) sequence of the TGFB latency-associated peptide, which frees TGFB to bind its cellular receptors. However, little is known about the role of integrins in the development of CP. We investigated the effects of small-molecule integrin inhibitors in a mouse model of CP...
July 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28126348/autophagy-is-required-for-activation-of-pancreatic-stellate-cells-associated-with-pancreatic-cancer-progression-and-promotes-growth-of-pancreatic-tumors-in-mice
#13
Sho Endo, Kohei Nakata, Kenoki Ohuchida, Shin Takesue, Hiromichi Nakayama, Toshiya Abe, Kazuhiro Koikawa, Takashi Okumura, Masafumi Sada, Kohei Horioka, Biao Zheng, Yusuke Mizuuchi, Chika Iwamoto, Masaharu Murata, Taiki Moriyama, Yoshihiro Miyasaka, Takao Ohtsuka, Kazuhiro Mizumoto, Yoshinao Oda, Makoto Hashizume, Masafumi Nakamura
BACKGROUND & AIMS: Pancreatic stellate cells (PSCs) change from a quiescent to activated state in the tumor environment and secrete extracellular matrix (ECM) molecules and cytokines to increase the aggressiveness of tumors. However, it is not clear how PSCs are activated to produce these factors, or whether this process can be inhibited. PSCs have morphological and functional similarities to hepatic stellate cells, which undergo autophagy to promote fibrosis and tumor growth. We investigated whether autophagy activates PSCs, which promotes development of the tumor stroma and growth of pancreatic tumors in mice...
January 23, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28109008/inhibition-of-group-1-p21-activated-kinases-suppresses-pancreatic-stellate-cell-activation-and-increases-survival-of-mice-with-pancreatic-cancer
#14
Dannel Yeo, Phoebe Phillips, Graham S Baldwin, Hong He, Mehrdad Nikfarjam
Pancreatic cancer remains one of the most lethal of all solid tumors. Pancreatic stellate cells (PSCs) are primarily responsible for the fibrosis that constitutes the stroma and p21-activated kinase 1 (PAK1) may have a role in signalling pathways involving PSCs. This study aimed to examine the role of PAK1 in PSCs and in the interaction of PSCs with pancreatic cancer cells. Human PSCs were isolated using the modified outgrowth method. The effect of inhibiting PAK1 with group 1 PAK inhibitor, FRAX597, on cell proliferation and apoptosis in vitro was measured by thymidine incorporation and annexin V assays, respectively...
May 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28099257/antifibrotic-effect-of-saturated-fatty-acids-via-endoplasmic-reticulum-stress-response-in-rat-pancreatic-stellate-cells
#15
Lingaku Lee, Tetsuhide Ito, Taichi Nakamura, Robert T Jensen, Hisato Igarashi, Ryoichi Takayanagi
OBJECTIVES: We investigated the effect of saturated fatty acids on chronic pancreatitis pathogenesis by elucidating the endoplasmic reticulum (ER) stress response in pancreatic stellate cells (PSCs), which are major effector cells in pancreatic fibrosis. METHODS: Wistar Bonn/Kobori rats were fed either control diet or high-fat diet (HFD) for 4 weeks. Meanwhile, cultured rat PSCs were stimulated with thapsigargin, an ER stress inducer, or palmitic acid (PA). Pancreatic fibrosis, expressions of fibrosis-related and ER stress-related proteins and mRNA, cell viability, and apoptosis were examined...
March 2017: Pancreas
https://www.readbyqxmd.com/read/28093281/kindlin-2-in-pancreatic-stellate-cells-promotes-the-progression-of-pancreatic-cancer
#16
Naoki Yoshida, Atsushi Masamune, Shin Hamada, Kazuhiro Kikuta, Tetsuya Takikawa, Fuyuhiko Motoi, Michiaki Unno, Tooru Shimosegawa
Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis associated with pancreatic ductal adenocarcinoma (PDAC). Kindlin-2 is a focal adhesion protein that regulates the activation of integrins. This study aimed to clarify the role of kindlin-2 in PSCs in pancreatic cancer. Kindlin-2 expression in 79 resected pancreatic cancer tissues was examined by immunohistochemical staining. Kindlin-2-knockdown immortalized human PSCs were established using small interfering RNA. Pancreatic cancer cells were treated with conditioned media of PSCs, and the cell proliferation and migration were examined...
April 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28092365/cancer-cell-chemokines-direct-chemotaxis-of-activated-stellate-cells-in-pancreatic-ductal-adenocarcinoma
#17
Ishan Roy, Kathleen A Boyle, Emily P Vonderhaar, Noah P Zimmerman, Egal Gorse, A Craig Mackinnon, Rosa F Hwang, Janusz Franco-Barraza, Edna Cukierman, Susan Tsai, Douglas B Evans, Michael B Dwinell
The mechanisms by which the extreme desmoplasia observed in pancreatic tumors develops remain unknown and its role in pancreatic cancer progression is unsettled. Chemokines have a key role in the recruitment of a wide variety of cell types in health and disease. Transcript and protein profile analyses of human and murine cell lines and human tissue specimens revealed a consistent elevation in the receptors CCR10 and CXCR6, as well as their respective ligands CCL28 and CXCL16. Elevated ligand expression was restricted to tumor cells, whereas receptors were in both epithelial and stromal cells...
March 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#18
E Hessmann, M S Patzak, L Klein, N Chen, V Kari, I Ramu, T E Bapiro, K K Frese, A Gopinathan, F M Richards, D I Jodrell, C Verbeke, X Li, R Heuchel, J M Löhr, S A Johnsen, T M Gress, V Ellenrieder, A Neesse
OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28024339/using-gold-nanoparticles-to-disrupt-the-tumor-microenvironment-an-emerging-therapeutic-strategy
#19
Jilian R Melamed, Rachel S Riley, Danielle M Valcourt, Emily S Day
Gold nanoparticles have received much attention recently as carriers for anticancer drugs and therapeutic oligonucleotides, but little research has investigated their potential to act as stand-alone therapeutics. Previous studies interrogating their short- and long-term systemic toxicity have found that although gold nanoparticles accumulate within and clear slowly from the liver and spleen, they do not appear to exert toxic effects in these organs. Interestingly, gold nanoparticles innately exhibit the ability to modulate the tumor microenvironment specifically by interfering with crosstalk between tumor cells and stromal cells...
December 27, 2016: ACS Nano
https://www.readbyqxmd.com/read/27977625/exosome-mediated-intercellular-communication-between-stellate-cells-and-cancer-cells-in-pancreatic-ductal-adenocarcinoma
#20
Aurelia Lugea, Richard T Waldron
No abstract text is available yet for this article.
January 2017: Pancreas
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