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pancreatic cancer PSCs

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https://www.readbyqxmd.com/read/27903970/ion-channels-in-control-of-pancreatic-stellate-cell-migration
#1
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...
November 26, 2016: 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
#2
Chiara Birtolo, Hung Pham, Susan Morvaridi, Chintan Chheda, Vay Liang W Go, Andrzej Ptasznik, Mouad Edderkaoui, Michael Weisman, Erika Noss, Michael 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...
November 14, 2016: 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
#3
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
#4
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
#5
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
#6
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...
October 18, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27758098/gold-nanoparticle-reprograms-pancreatic-tumor-microenvironment-and-inhibits-tumor-growth
#7
Sounik Saha, Xunhao Xiong, Prabir K Chakraborty, Khader Shameer, Rochelle R Arvizo, Rachel A Kudgus, Shailendra Kumar Dhar Dwivedi, Md Nazir Hossen, Elizabeth M Gillies, J David Robertson, Joel T Dudley, Raul A Urrutia, Russell G Postier, Resham Bhattacharya, Priyabrata Mukherjee
Altered tumor microenvironment (TME) arising from a bidirectional crosstalk between the pancreatic cancer cells (PCCs) and the pancreatic stellate cells (PSCs) is implicated in the dismal prognosis in pancreatic ductal adenocarcinoma (PDAC), yet effective strategies to disrupt the crosstalk is lacking. Here, we demonstrate that gold nanoparticles (AuNPs) inhibit proliferation and migration of both PCCs and PSCs by disrupting the bidirectional communication via alteration of the cell secretome. Analyzing the key proteins identified from a functional network of AuNP-altered secretome in PCCs and PSCs, we demonstrate that AuNPs impair secretions of major hub node proteins in both cell types and transform activated PSCs toward a lipid-rich quiescent phenotype...
October 19, 2016: ACS Nano
https://www.readbyqxmd.com/read/27696296/periostin-promotes-the-chemotherapy-resistance-to-gemcitabine-in-pancreatic-cancer
#8
Yang Liu, Fan Li, Feng Gao, Lingxi Xing, Peng Qin, Xingxin Liang, Jiajie Zhang, Xiaohui Qiao, Lizhou Lin, Qian Zhao, Lianfang Du
Pancreatic ductal adenocarcinoma (PDAC) ranks fourth among cancer-related deaths. The nucleoside analog gemcitabine has been the cornerstone of adjuvant chemotherapy in PDAC for decades. However, gemcitabine resistance develops within weeks of chemotherapy initiation, which might be intrinsic to cancer cells and influenced by tumor microenvironment. Recently, pancreatic stellate cells (PSCs) have greatly increased our attention on tumor microenvironment-mediated drug resistance. Periostin is exclusively overexpressed in PSCs and the stroma of PDAC creating a tumor-supportive microenvironment in the pancreas...
September 30, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27670661/role-of-trpc1-channels-in-pressure-mediated-activation-of-murine-pancreatic-stellate-cells
#9
Benedikt Fels, Nikolaj Nielsen, Albrecht Schwab
The tumor environment contributes importantly to tumor cell behavior and cancer progression. Aside from biochemical constituents, physical factors of the environment also influence the tumor. Growing evidence suggests that mechanics [e.g., tumor (stroma) elasticity, tissue pressure] are critical players of cancer progression. Underlying mechanobiological mechanisms involve among others the regulation of focal adhesion molecules, cytoskeletal modifications, and mechanosensitive (MS) ion channels of cancer- and tumor-associated cells...
October 2016: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/27627810/generation-of-an-in%C3%A2-vitro-3d-pdac-stroma-rich-spheroid-model
#10
Matthew J Ware, Vazrik Keshishian, Justin J Law, Jason C Ho, Carlos A Favela, Paul Rees, Billie Smith, Sayeeduddin Mohammad, Rosa F Hwang, Kimal Rajapakshe, Cristian Coarfa, Shixia Huang, Dean P Edwards, Stuart J Corr, Biana Godin, Steven A Curley
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent desmoplastic/stromal reaction, which contributes to the poor clinical outcome of this disease. Therefore, greater understanding of the stroma development and tumor-stroma interactions is highly required. Pancreatic stellate cells (PSC) are myofibroblast-like cells located in exocrine areas of the pancreas, which as a result of inflammation produced by PDAC migrate and accumulate in the tumor mass, secreting extracellular matrix components and producing the dense PDAC stroma...
November 2016: Biomaterials
https://www.readbyqxmd.com/read/27609457/honokiol-suppresses-pancreatic-tumor-growth-metastasis-and-desmoplasia-by-interfering-with-tumor-stromal-cross-talk
#11
Courey Averett, Arun Bhardwaj, Sumit Arora, Sanjeev K Srivastava, Mohammad Aslam Khan, Aamir Ahmad, Seema Singh, James E Carter, Moh'd Khushman, Ajay P Singh
The poor clinical outcome of pancreatic cancer (PC) is largely attributed to its aggressive nature and refractoriness to currently available therapeutic modalities. We previously reported antitumor efficacy of honokiol (HNK), a phytochemical isolated from various parts of Magnolia plant, against PC cells in short-term in vitro growth assays. Here, we report that HNK reduces plating efficiency and anchorage-independent growth of PC cells and suppresses their migration and invasiveness. Furthermore, significant inhibition of pancreatic tumor growth by HNK is observed in orthotopic mouse model along with complete-blockage of distant metastases...
September 8, 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27604902/tgf-%C3%AE-induced-stromal-cyr61-promotes-resistance-to-gemcitabine-in-pancreatic-ductal-adenocarcinoma-through-downregulation-of-the-nucleoside-transporters-hent1-and-hcnt3
#12
Rachel A Hesler, Jennifer J Huang, Mark D Starr, Victoria M Treboschi, Alyssa G Bernanke, Andrew B Nixon, Shannon J McCall, Rebekah R White, Gerard C Blobe
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer in part due to inherent resistance to chemotherapy, including the first-line drug gemcitabine. Although low expression of the nucleoside transporters hENT1 and hCNT3 that mediate cellular uptake of gemcitabine has been linked to gemcitabine resistance, the mechanisms regulating their expression in the PDAC tumor microenvironment are largely unknown. Here, we report that the matricellular protein cysteine-rich angiogenic inducer 61 (CYR61) negatively regulates the nucleoside transporters hENT1 and hCNT3...
September 7, 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27602757/pancreatic-stellate-cell-secreted-il-6-stimulates-stat3-dependent-invasiveness-of-pancreatic-intraepithelial-neoplasia-and-cancer-cells
#13
Nagaraj S Nagathihalli, Jason A Castellanos, Michael N VanSaun, Xizi Dai, Mahogany Ambrose, Qiaozhi Guo, Yanhua Xiong, Nipun B Merchant
Pancreatic ductal adenocarcinoma (PDAC) is a dynamic tumor supported by several stromal elements such as pancreatic stellate cells (PSC). Significant crosstalk exists between PSCs and tumor cells to stimulate oncogenic signaling and malignant progression of PDAC. However, how PSCs activate intercellular signaling in PDAC cells remains to be elucidated. We have previously shown that activated signal transducer and activator of transcription 3 (STAT3) signaling is a key component in the progression of pancreatic neoplasia...
September 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27600527/atra-mechanically-reprograms-pancreatic-stellate-cells-to-suppress-matrix-remodelling-and-inhibit-cancer-cell-invasion
#14
Antonios Chronopoulos, Benjamin Robinson, Muge Sarper, Ernesto Cortes, Vera Auernheimer, Dariusz Lachowski, Simon Attwood, Rebeca García, Saba Ghassemi, Ben Fabry, Armando Del Río Hernández
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal survival rate. Persistent activation of pancreatic stellate cells (PSCs) can perturb the biomechanical homoeostasis of the tumour microenvironment to favour cancer cell invasion. Here we report that ATRA, an active metabolite of vitamin A, restores mechanical quiescence in PSCs via a mechanism involving a retinoic acid receptor beta (RAR-β)-dependent downregulation of actomyosin (MLC-2) contractility. We show that ATRA reduces the ability of PSCs to generate high traction forces and adapt to extracellular mechanical cues (mechanosensing), as well as suppresses force-mediated extracellular matrix remodelling to inhibit local cancer cell invasion in 3D organotypic models...
September 7, 2016: Nature Communications
https://www.readbyqxmd.com/read/27573419/activated-leukocyte-cell-adhesion-molecule-regulates-the-interaction-between-pancreatic-cancer-cells-and-stellate-cells
#15
Wei-Wei Zhang, Shu-Hui Zhan, Chang-Xin Geng, Xin Sun, Mert Erkan, Jörg Kleeff, Xiang-Jun Xie
Activated leukocyte cell adhesion molecule (ALCAM/CD166) is a transmembrane glycoprotein that is involved in tumor progression and metastasis. In the present study, the expression and functional role of ALCAM in pancreatic cancer cells and pancreatic stellate cells (PSCs) was investigated. Tissue specimens were obtained from patients with pancreatic ductal adenocarcinoma (n=56) or chronic pancreatitis (CP; n=10), who underwent pancreatic resection, and from normal pancreatic tissue samples (n=10). Immunohistochemistry was used to analyze the localization and expression of ALCAM in pancreatic tissues...
October 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27564263/role-of-microenvironmental-periostin-in-pancreatic-cancer-progression
#16
Yang Liu, Fan Li, Feng Gao, Lingxi Xing, Peng Qin, Xingxin Liang, Jiajie Zhang, Xiaohui Qiao, Lizhou Lin, Qian Zhao, Lianfang Du
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent desmoplastic reaction. Pancreatic stellate cells (PSCs) are the principal effector cells responsible for stroma production. Aberrant up-regulation of periostin expression has been reported in activated PSCs. In this study, we investigated the role of periostin and the mechanisms underlying its aberrant upregulation in PDAC. We used lentiviral shRNA and human recombinant periostin protein to down and up regulate periostin expression in vitro...
August 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27513892/targeting-of-the-p2x7-receptor-in-pancreatic-cancer-and-stellate-cells
#17
Andrea Giannuzzo, Mara Saccomano, Joanna Napp, Maria Ellegaard, Frauke Alves, Ivana Novak
The ATP-gated receptor P2X7 (P2X7R) is involved in regulation of cell survival and has been of interest in cancer field. Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer and new markers and therapeutic targets are needed. PDAC is characterized by a complex tumour microenvironment, which includes cancer and pancreatic stellate cells (PSCs), and potentially high nucleotide/side turnover. Our aim was to determine P2X7R expression and function in human pancreatic cancer cells in vitro as well as to perform in vivo efficacy study applying P2X7R inhibitor in an orthotopic xenograft mouse model of PDAC...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27509858/pancreatic-stellate-cells-support-tumour-metabolism-through-autophagic-alanine-secretion
#18
Cristovão M Sousa, Douglas E Biancur, Xiaoxu Wang, Christopher J Halbrook, Mara H Sherman, Li Zhang, Daniel Kremer, Rosa F Hwang, Agnes K Witkiewicz, Haoqiang Ying, John M Asara, Ronald M Evans, Lewis C Cantley, Costas A Lyssiotis, Alec C Kimmelman
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA)...
August 25, 2016: Nature
https://www.readbyqxmd.com/read/27488376/nitric-oxide-signals-are-interlinked-with-calcium-signals-in-normal-pancreatic-stellate-cells-upon-oxidative-stress-and-inflammation
#19
Monika A Jakubowska, Pawel E Ferdek, Oleg V Gerasimenko, Julia V Gerasimenko, Ole H Petersen
The mammalian diffuse stellate cell system comprises retinoid-storing cells capable of remarkable transformations from a quiescent to an activated myofibroblast-like phenotype. Activated pancreatic stellate cells (PSCs) attract attention owing to the pivotal role they play in development of tissue fibrosis in chronic pancreatitis and pancreatic cancer. However, little is known about the actual role of PSCs in the normal pancreas. These enigmatic cells have recently been shown to respond to physiological stimuli in a manner that is markedly different from their neighbouring pancreatic acinar cells (PACs)...
August 2016: Open Biology
https://www.readbyqxmd.com/read/27487486/the-calpain-inhibitor-calpeptin-suppresses-pancreatic-cancer-by-disrupting-cancer-stromal-interactions-in-a-mouse-xenograft-model
#20
Masaki Yoshida, Yoshihiro Miyasaka, Kenoki Ohuchida, Takashi Okumura, Biao Zheng, Nobuhiro Torata, Hayato Fujita, Toshinaga Nabae, Tatsuya Manabe, Masaya Shimamoto, Takao Ohtsuka, Kazuhiro Mizumoto, Masafumi Nakamura
Desmoplasia contributes to the aggressive behavior of pancreatic cancer. However, recent clinical trials testing several anti-fibrotic agents on pancreatic cancer have not shown clear efficacy. Therefore, further investigation of desmoplasia-targeting anti-fibrotic agents by another mechanism is needed. Calpeptin, an inhibitor of calpains, suppressed fibroblast function and inhibited fibrosis. In this study, we investigated the anticancer effects of calpeptin on pancreatic cancer. We investigated whether calpeptin inhibited tumor progression using a mouse xenograft model...
August 3, 2016: Cancer Science
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