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pancreatic cancer PSCs

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https://www.readbyqxmd.com/read/28540429/identification-of-markers-for-quiescent-pancreatic-stellate-cells-in-the-normal-human-pancreas
#1
Michael Friberg Bruun Nielsen, Michael Bau Mortensen, Sönke Detlefsen
Pancreatic stellate cells (PSCs) play a central role as source of fibrogenic cells in pancreatic cancer and chronic pancreatitis. In contrast to quiescent hepatic stellate cells (qHSCs), a specific marker for quiescent PSCs (qPSCs) that can be used in formalin-fixed and paraffin embedded (FFPE) normal human pancreatic tissue has not been identified. The aim of this study was to identify a marker enabling the identification of qPSCs in normal human FFPE pancreatic tissue. Immunohistochemical (IHC), double-IHC, immunofluorescence (IF) and double-IF analyses were carried out using a tissue microarray consisting of cores with normal human pancreatic tissue...
May 25, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28461158/pancreatic-stellate-cells-increase-pancreatic-cancer-cells-invasion-through-the-hepatocyte-growth-factor-c-met-survivin-regulated-by-p53-p21
#2
Xiao-Peng Yang, Shang-Long Liu, Jian-Fei Xu, Shou-Gen Cao, Yu Li, Yan-Bing Zhou
Pancreatic stellate cells (PSCs) are a key cellular component of the pancreatic tumor microenvironment and are considered to contribute to tumor invasion and metastasis. Multiple cytokines and growth factors derived from PSCs are involved in malignant cancer progression, including hepatocyte growth factor (HGF). However, the molecular mechanisms by which HGF regulates cancer invasion and metastasis have not been completely elucidated. Here, we report that two pancreatic cancer (PC) cell lines, Panc-1 and SW1990, displayed different invasive and migratory abilities after treatment with HGF secreted by PSCs...
April 29, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28400334/asporin-promotes-pancreatic-cancer-cell-invasion-and-migration-by-regulating-the-epithelial-to-mesenchymal-transition-emt-through-both-autocrine-and-paracrine-mechanisms
#3
Lili Wang, Huanwen Wu, Li Wang, Hui Zhang, Junliang Lu, Zhiyong Liang, Tonghua Liu
Pancreatic cancer is histopathologically characterized by excessive desmoplasia induced by pancreatic stellate cells (PSCs). Asporin, an extracellular matrix (ECM) protein, is highly expressed in cancer-associated fibroblasts (CAFs). Asporin expression in PSCs and its roles in PSC-pancreatic cancer cell (PCC) interaction remain unclear. The present study firstly showed that Asporin is highly expressed in activated PSCs and is involved in PSC-mediated invasion and migration of PCCs. Exogenous Asporin interacted with the transmembrane receptor CD44 on PCCs to activate NF-κB/p65 and promoted the epithelial-mesenchymal transition (EMT) in PCCs...
July 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28379317/circulating-pancreatic-stellate-stromal-cells-in-pancreatic-cancer-a-fertile-area-for-novel-research
#4
Tony Cy Pang, Zhihong Xu, Srinivasa Pothula, Therese Becker, David Goldstein, Romano C Pirola, Jeremy S Wilson, Minoti V Apte
Pancreatic stellate cells (PSCs) is known to play an important role in facilitating pancreatic cancer progression - both in terms of local tumour growth as well as the establishment of metastases. We have previously demonstrated that PSCs from the primary cancer seed to distant metastatic sites. We therefore hypothesise that PSCs circulate along with pancreatic cancer cells (circulating tumour cells - CTCs) to help create a growth permissive microenvironment at distant metastatic sites. This review aims to explore the concept of circulating PSCs in pancreatic cancer and suggests future directions for research in this area...
April 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28336327/galectin-1-driven-upregulation-of-sdf-1-in-pancreatic-stellate-cells-promotes-pancreatic-cancer-metastasis
#5
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 21, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28281184/tgf-%C3%AE-1-mir-200a-pten-induces-epithelial-mesenchymal-transition-and-fibrosis-of-pancreatic-stellate-cells
#6
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/28217371/pathogenic-mechanisms-of-pancreatitis
#7
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
#8
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/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/28126348/autophagy-is-required-for-activation-of-pancreatic-stellate-cells-associated-with-pancreatic-cancer-progression-and-promotes-growth-of-pancreatic-tumors-in-mice
#11
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 morphologic 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...
May 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
#12
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/28093281/kindlin-2-in-pancreatic-stellate-cells-promotes-the-progression-of-pancreatic-cancer
#13
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/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#14
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/27903970/ion-channels-in-control-of-pancreatic-stellate-cell-migration
#15
Hannah Storck, Benedikt Hild, Sandra Schimmelpfennig, Sarah Sargin, Nikolaj Nielsen, Angela Zaccagnino, Thomas Budde, Ivana Novak, Holger Kalthoff, Albrecht Schwab
Pancreatic stellate cells (PSCs) play a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC). Once activated, PSCs support proliferation and metastasis of carcinoma cells. PSCs even co-metastasise with carcinoma cells. This requires the ability of PSCs to migrate. In recent years, it has been established that almost all "hallmarks of cancer" such as proliferation or migration/invasion also rely on the expression and function of ion channels. So far, there is only very limited information about the function of ion channels in PSCs...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27855278/cadherin-11-is-a-cell-surface-marker-up-regulated-in-activated-pancreatic-stellate-cells-and-is-involved-in-pancreatic-cancer-cell-migration
#16
Chiara Birtolo, Hung Pham, Susan Morvaridi, Chintan Chheda, Vay Liang W Go, Andrzej Ptasznik, Mouad Edderkaoui, Michael H Weisman, Erika Noss, Michael B Brenner, Brent Larson, Maha Guindi, Qiang Wang, Stephen J Pandol
Chronic pancreatitis is a prominent risk factor for the development of pancreatic ductal adenocarcinoma. In both conditions, the activation of myofibroblast-like pancreatic stellate cells (PSCs) plays a predominant role in the formation of desmoplastic reaction through the synthesis of connective tissue and extracellular matrix, inducing local pancreatic fibrosis and an inflammatory response. Yet the signaling events involved in chronic pancreatitis and pancreatic cancer progression and metastasis remain poorly defined...
January 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/27819128/human-pancreatic-stellate-cells-modulate-3d-collagen-alignment-to-promote-the-migration-of-pancreatic-ductal-adenocarcinoma-cells
#17
Cole R Drifka, Agnes G Loeffler, Corinne R Esquibel, Sharon M Weber, Kevin W Eliceiri, W John Kao
A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the ability for cancer cells to aggressively infiltrate and navigate through a dense stroma during the metastatic process. Key features of the PDAC stroma include an abundant population of activated pancreatic stellate cells (PSCs) and highly aligned collagen fibers; however, important questions remain regarding how collagen becomes aligned and what the biological manifestations are. To better understand how PSCs, aligned collagen, and PDAC cells might cooperate during the transition to invasion, we utilized a microchannel-based in vitro tumor model and advanced imaging technologies to recreate and examine in vivo-like heterotypic interactions...
December 2016: Biomedical Microdevices
https://www.readbyqxmd.com/read/27797936/il-6-and-pd-l1-antibody-blockade-combination-therapy-reduces-tumour-progression-in-murine-models-of-pancreatic-cancer
#18
Thomas A Mace, Reena Shakya, Jason R Pitarresi, Benjamin Swanson, Christopher W McQuinn, Shannon Loftus, Emily Nordquist, Zobeida Cruz-Monserrate, Lianbo Yu, Gregory Young, Xiaoling Zhong, Teresa A Zimmers, Michael C Ostrowski, Thomas Ludwig, Mark Bloomston, Tanios Bekaii-Saab, Gregory B Lesinski
OBJECTIVE: Limited efficacy of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) has prompted investigation into combination therapy. We hypothesised that interleukin 6 (IL-6) blockade would modulate immunological features of PDAC and enhance the efficacy of anti-programmed death-1-ligand 1 (PD-L1) checkpoint inhibitor therapy. DESIGN: Transcription profiles and IL-6 secretion from primary patient-derived pancreatic stellate cells (PSCs) were analyzed via Nanostring and immunohistochemistry, respectively...
October 21, 2016: Gut
https://www.readbyqxmd.com/read/27773749/desmoplasia-suppression-by-metformin-mediated-ampk-activation-inhibits-pancreatic-cancer-progression
#19
Wanxing Duan, Ke Chen, Zhengdong Jiang, Xin Chen, Liankang Sun, Jiahui Li, Jianjun Lei, Qinhong Xu, Jiguang Ma, Xuqi Li, Liang Han, Zheng Wang, Zheng Wu, Fengfei Wang, Erxi Wu, Qingyong Ma, Zhenhua Ma
Emerging evidence suggests that metformin, an activator of AMP-activated protein kinase (AMPK), may be useful in preventing and treating pancreatic ductal adenocarcinoma (PDAC). However, whether metformin has an effect on the stromal reaction of PDAC remains unknown. In this study, we first evaluated the expression of AMPK and phosphorylated-AMPK (P-AMPK) in normal and PDAC tissues, our data indicate that reduced P-AMPK expression is a frequent event in PDAC and correlated with poor prognosis and the dense stromal reaction...
January 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27769941/enzyme-mediated-stiffening-hydrogels-for-probing-activation-of-pancreatic-stellate-cells
#20
Hung-Yi Liu, Tanja Greene, Tsai-Yu Lin, Camron S Dawes, Murray Korc, Chien-Chi Lin
The complex network of biochemical and biophysical cues in the pancreatic desmoplasia not only presents challenges to the fundamental understanding of tumor progression, but also hinders the development of therapeutic strategies against pancreatic cancer. Residing in the desmoplasia, pancreatic stellate cells (PSCs) are the major stromal cells affecting the growth and metastasis of pancreatic cancer cells by means of paracrine effects and extracellular matrix protein deposition. PSCs remain in a quiescent/dormant state until they are 'activated' by various environmental cues...
January 15, 2017: Acta Biomaterialia
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