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Pancreatic stellate cell

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https://www.readbyqxmd.com/read/28615524/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#1
Jonas R M Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M J Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L J Smits
Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC)...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28605029/the-pancreatic-cancer-microenvironment-a-true-double-agent
#2
REVIEW
Laleh G Melstrom, Marcela D Salazar, Don J Diamond
The tumor microenvironment in pancreatic cancer is a complex balance of pro- and anti-tumor components. The dense desmoplasia consists of immune cells, extracellular matrix, growth factors, cytokines, and cancer associated fibroblasts (CAF) or pancreatic stellate cells (PSC). There are a multitude of targets including hyaluronan, angiogenesis, focal adhesion kinase (FAK), connective tissue growth factor (CTGF), CD40, chemokine (C-X-C motif) receptor 4 (CXCR-4), immunotherapy, and Vitamin D. The developing clinical therapeutics will be reviewed...
June 12, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28601475/pancreatic-stellate-cells-in-pancreatic-cancer-in-focus
#3
REVIEW
A Allam, A R Thomsen, M Gothwal, D Saha, J Maurer, T B Brunner
Pancreatic stellate cells are stromal cells that have multiple physiological functions such as the production of extracellular matrix, stimulation of amylase secretion, phagocytosis and immunity. In pancreatic cancer, stellate cells exhibit a different myofibroblastic-like morphology with the expression of alpha-smooth muscle actin, the activated form is engaged in several mechanisms that support tumorigenesis and cancer invasion and progression. In contrast to the aforementioned observations, eliminating the stromal cells that are positive for alpha-smooth muscle actin resulted in immune-evasion of the cancer cells and resulted in worse prognosis in animal models...
May 27, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28590306/pancreatic-stellate-cells-what-s-new
#4
Tony C Y Pang, Jeremy S Wilson, Minoti V Apte
PURPOSE OF REVIEW: Pancreatic stellate cells (PSCs) play an integral role in the pathogenesis of pancreatitis and pancreatic cancer. With the developing knowledge of this important cell type, we are at the cusp of developing effective therapies for the above diseases based upon targeting the PSC and modulating its function. RECENT FINDINGS: The major themes of the recent PSC literature include: PSC interactions with the extracellular matrix and other stromal components; intracellular calcium physiology as drivers of mechanical interactions and necrosis; the relationship between proinflammatory, protumoural, angiogenic, and metabolic pathways in pancreatic necrosis, fibrosis, and carcinogenesis; and targeting of the stroma for antitumoural and antifibrotic effects...
June 5, 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/28566691/substrate-rigidity-controls-activation-and-durotaxis-in-pancreatic-stellate-cells
#5
Dariusz Lachowski, Ernesto Cortes, Daniel Pink, Antonios Chronopoulos, Saadia A Karim, Jennifer P Morton, Armando E Del Río Hernández
Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive malignancy characterised by the presence of extensive desmoplasia, thought to be responsible for the poor response of patients to systemic therapies. Pancreatic stellate cells (PSCs) are key mediators in the production of this fibrotic stroma, upon activation transitioning to a myofibroblast-like, high matrix secreting phenotype. Given their importance in disease progression, characterisation of PSC activation has been extensive, however one aspect that has been overlooked is the mechano-sensing properties of the cell...
May 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28552244/ca-2-signalling-underlying-pancreatitis
#6
REVIEW
J V Gerasimenko, S Peng, T Tsugorka, O V Gerasimenko
In spite of significant scientific progress in recent years, acute pancreatitis (AP) is still a dangerous and in up to 5% of cases deadly disease with no specific cure. It is self-resolved in the majority of cases, but could result in chronic pancreatitis (CP) and increased risk of pancreatic cancer (PC). One of the early events in AP is premature activation of digestive pro-enzymes, including trypsinogen, inside pancreatic acinar cells (PACs) due to an excessive rise in the cytosolic Ca(2+) concentration, which is the result of Ca(2+) release from internal stores followed by Ca(2+) entry through the store operated Ca(2+) channels in the plasma membrane...
May 18, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28551708/novel-and-experimental-therapies-in-chronic-pancreatitis
#7
REVIEW
Soumya Jagannath, Pramod Kumar Garg
Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas. The currently available treatment of CP is aimed at controlling symptoms and managing complications. Unfortunately, no specific treatment is available to halt the progression of the disease process because the pathophysiological perturbations in CP are not well understood. In this review, we discuss various therapeutic targets and investigational agents acting on these targets. Among these, therapies modulating immune cells and those acting on pancreatic stellate cells appear promising and may translate into clinical benefit in near future...
May 27, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28549346/functional-heterogeneity-in-tumor-derived-human-pancreatic-stellate-cells-differential-expression-of-hgf-and-implications-for-mitogenic-signaling-and-migration-in-pancreatic-cancer-cells
#8
Vegard Tjomsland, Monica Aasrum, Thoralf Christoffersen, Ivar P Gladhaug
The pancreatic stellate cell (PSC) is the principal cell type of the desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC). PSCs interact with cancer cells and influence the progression of the disease through a complex network of signaling molecules including hepatocyte growth factor (HGF). Functional heterogeneity of PSCs within a tumor might conceivably influence tumor progression. We investigated PSC populations isolated from different human PDACs and examined the effects of PSC-conditioned medium on BxPC-3 and AsPC-1 pancreatic cancer cells...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28540429/identification-of-markers-for-quiescent-pancreatic-stellate-cells-in-the-normal-human-pancreas
#9
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/28538690/dysregulation-of-mirna-expression-in-cancer-associated-fibroblasts-cafs-and-its-consequences-on-the-tumor-microenvironment
#10
REVIEW
Maren Schoepp, Anda Jana Ströse, Jörg Haier
The tumor microenvironment, including cancer-associated fibroblasts (CAF), has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell-tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles...
May 24, 2017: Cancers
https://www.readbyqxmd.com/read/28536305/shaping-the-tumor-stroma-and-sparking-immune-activation-by-cd40-and-4-1bb-signaling-induced-by-an-armed-oncolytic-virus
#11
Emma Eriksson, Ioanna Milenova, Jessica Wenthe, Magnus Ståhle, Justyna Leja-Jarblad, Gustav Ullenhag, Anna Dimberg, Rafael Moreno, Ramon Alemany, Angelica Loskog
PURPOSE: Pancreatic cancer is a severe indication with short expected survival despite surgery and/or combination chemotherapeutics. Checkpoint blockade antibodies are approved for several cancer indications but pancreatic cancer has remained refractory. However, there are clinical data suggesting that stimulation of the CD40 pathway may be of interest for these patients. Oncolytic viruses armed with immunostimulatory genes represent an interesting approach. Herein we present LOAd703, a designed adenovirus armed with trimerized CD40L and 4-1BBL that activate the CD40 and 4-1BB pathways, respectively...
May 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28534517/prolonged-exposure-to-extracellular-lumican-restrains-pancreatic-adenocarcinoma-growth
#12
X Li, Y Kang, D Roife, Y Lee, M Pratt, M R Perez, B Dai, E J Koay, J B Fleming
We previously demonstrated that pancreatic stellate cells within pancreatic ductal adenocarcinoma (PDAC) stroma secrete lumican and its presence is associated with prolonged survival of patients with localized PDAC. Here, we observed that extracellular lumican decreases PDAC tumour cell growth in xenograft and syngeneic orthotopic animal models, and induces growth inhibition of low-passage human PDAC cells in a species-specific manner. PDAC cells grown in variant culture conditions and exposed to extracellular lumican display typical characterizations of cancer cell in a quiescent state, such as growth inhibition, apoptosis, G0/G1 arrest and chemoresistance...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28524768/anti-microrna-targeting-using-peptide-based-nanocomplexes-to-inhibit-differentiation-of-human-pancreatic-stellate-cells
#13
Jonas Schnittert, Praneeth R Kuninty, Tomasz F Bystry, Roland Brock, Gert Storm, Jai Prakash
AIM: To develop novel peptide-based nanocomplexes (NCs) for delivery of anti-miRNA oligonucleotides to human-derived pancreatic stellate cells (hPSCs), precursors of cancer-associated fibroblasts. MATERIALS & METHODS: NCs of anti-miRNA oligonucleotides and cell-penetrating peptides (different variants) were formed and characterized. The effects of anti-miR-199a delivery on hPSC differentiation and 3D heterospheroid formation were investigated. RESULTS: Dimeric cell-penetrating peptide based NCs (NC-2) showed 130-fold higher uptake by hPSCs compared with monomer-based NCs (NC-1) and tenfold higher uptake compared with general fibroblasts and different pancreatic tumor cells...
May 19, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28524160/stroma-regulated-hmga2-is-an-independent-prognostic-marker-in-pdac-and-aac
#14
Carina Strell, Karin Jessica Norberg, Artur Mezheyeuski, Jonas Schnittert, Praneeth R Kuninty, Carlos Fernández Moro, Janna Paulsson, Nicolai Aagaard Schultz, Dan Calatayud, Johannes Matthias Löhr, Oliver Frings, Caroline Sophie Verbeke, Rainer Lothar Heuchel, Jai Prakash, Julia Sidenius Johansen, Arne Östman
BACKGROUND: The HMGA2 protein has experimentally been linked to EMT and cancer stemness. Recent studies imply that tumour-stroma interactions regulate these features and thereby contribute to tumour aggressiveness. METHODS: We analysed 253 cases of pancreatic ductal adenocarcinoma (PDAC) and 155 cases of ampullary adenocarcinoma (AAC) for HMGA2 expression by IHC. The data were correlated with stroma abundance and supplemented by experimental studies. RESULTS: HMGA2 acts as an independent prognostic marker associated with a significantly shorter overall survival in both tumour types...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28506430/george-e-palade-memorial-lecture-my-life-in-pancreatic-research-unexpected-results-may-open-the-door
#15
REVIEW
Makoto Otsuki
The Palade Prize is the most distinguished award of the IAP for achievement in pancreatic research. It is named after George E. Palade, who in 1974 was awarded the Nobel Prize for his work on protein trafficking in pancreatic acinar cells. It is a great honor to be awarded the 2016 Palade Prize. While I was in graduate school, I was conducting research on hypothalamo-pituitary-thyroid axis; after finishing graduate school, I began research on amylase isoenzymes. This was the first step of my pancreatic research...
May 6, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28496202/inhibition-of-jak-stat-signaling-reduces-the-activation-of-pancreatic-stellate-cells-in-vitro-and-limits-caerulein-induced-chronic-pancreatitis-in-vivo
#16
Hannah M Komar, Gregory Serpa, Claire Kerscher, Erin Schwoegl, Thomas A Mace, Ming Jin, Ming-Chen Yang, Ching-Shih Chen, Mark Bloomston, Michael C Ostrowski, Phil A Hart, Darwin L Conwell, Gregory B Lesinski
Chronic pancreatitis (CP) is a fibro-inflammatory disease leading to pain, maldigestion, and pancreatic insufficiency. No therapeutic options exist due to a limited understanding of the biology of CP pathology. Recent findings implicate pancreatic stellate cells (PSC) as prominent mediators of inflammatory and fibrotic processes during CP. Here, we utilized primary and immortalized PSC obtained from mice and patients with CP or pancreatic cancer to examine the effect of Jak/STAT and MAPK pathway inhibition in vitro...
May 11, 2017: Scientific Reports
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
#17
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...
August 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28442507/protein-kinase-stk25-aggravates-the-severity-of-non-alcoholic-fatty-pancreas-disease-in-mice
#18
Esther Nunez Duran, Belen Chanclon, Silva Sütt, Joana Real, Hanns-Ulrich Marschall, Ingrid Wernstedt-Asterholm, Emelie Cansby, Margit Mahlapuu
Characterising the molecular networks that negatively regulate pancreatic β-cell function is essential for understanding the underlying pathogenesis and developing new treatment strategies for type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a critical regulator of ectopic fat storage, meta-inflammation, and fibrosis in liver and skeletal muscle. Here, we assessed the role of STK25 in control of progression of non-alcoholic fatty pancreas disease in the context of chronic exposure to dietary lipids in mice...
April 25, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28439020/mathematical-model-of-chronic-pancreatitis
#19
Wenrui Hao, Hannah M Komar, Phil A Hart, Darwin L Conwell, Gregory B Lesinski, Avner Friedman
Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas, leading to its fibrotic destruction. There are currently no drugs that can stop or slow the progression of the disease. The etiology of the disease is multifactorial, whereas recurrent attacks of acute pancreatitis are thought to precede the development of CP. A better understanding of the pathology of CP is needed to facilitate improved diagnosis and treatment strategies for this disease. The present paper develops a mathematical model of CP based on a dynamic network that includes macrophages, pancreatic stellate cells, and prominent cytokines that are present at high levels in the CP microenvironment...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28407685/extra-pancreatic-invasion-induces-lipolytic-and-fibrotic-changes-in-the-adipose-microenvironment-with-released-fatty-acids-enhancing-the-invasiveness-of-pancreatic-cancer-cells
#20
Takashi Okumura, Kenoki Ohuchida, Masafumi Sada, Toshiya Abe, Sho Endo, Kazuhiro Koikawa, Chika Iwamoto, Daisuke Miura, Yusuke Mizuuchi, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Tatsuya Manabe, Takao Ohtsuka, Eishi Nagai, Kazuhiro Mizumoto, Yoshinao Oda, Makoto Hashizume, Masafumi Nakamura
Pancreatic cancer progression involves components of the tumor microenvironment, including stellate cells, immune cells, endothelial cells, and the extracellular matrix. Although peripancreatic fat is the main stromal component involved in extra-pancreatic invasion, its roles in local invasion and metastasis of pancreatic cancer remain unclear. This study investigated the role of adipose tissue in pancreatic cancer progression using genetically engineered mice (Pdx1-Cre; LSL-KrasG12D; Trp53R172H/+) and an in vitro model of organotypic fat invasion...
March 14, 2017: Oncotarget
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