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Pancreatic stellate cell

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https://www.readbyqxmd.com/read/29329547/microfluidic-co-culture-of-pancreatic-tumor-spheroids-with-stellate-cells-as-a-novel-3d-model-for-investigation-of%C3%A2-stroma-mediated-cell-motility-and-drug-resistance
#1
Ji-Hyun Lee, Seul-Ki Kim, Iftikhar Ali Khawar, Su-Yeong Jeong, Seok Chung, Hyo-Jeong Kuh
BACKGROUND: Pancreatic stellate cells (PSCs), a major component of the tumor microenvironment in pancreatic cancer, play roles in cancer progression as well as drug resistance. Culturing various cells in microfluidic (microchannel) devices has proven to be a useful in studying cellular interactions and drug sensitivity. Here we present a microchannel plate-based co-culture model that integrates tumor spheroids with PSCs in a three-dimensional (3D) collagen matrix to mimic the tumor microenvironment in vivo by recapitulating epithelial-mesenchymal transition and chemoresistance...
January 12, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29328490/galectin-1-expression-in-activated-pancreatic-satellite-cells-promotes-fibrosis-in-chronic-pancreatitis-pancreatic-cancer-via-the-tgf-%C3%AE-1-smad-pathway
#2
Dong Tang, Qi Wu, Jingqiu Zhang, Hongpeng Zhang, Zhongxu Yuan, Jiaming Xu, Yang Chong, Yuqin Huang, Qingquan Xiong, Sen Wang, Ying Tian, Yongdie Lu, Xiao Ge, Wenjing Shen, Daorong Wang
Chronic pancreatitis/pancreatic cancer (CP/PC) is characterized by fibrous connective tissue proliferation induced by activated pancreatic stellate cells (PSCs). Galectin-1 is upregulated in activated PSCs and is important for the continuing activation of PSCs. The aim of this study was to evaluate the effect of galectin-1 derived from activated PSCs on the progression of fibrosis in CP/PC. To this end, the expression of desmin, α-SMA, galectin-1, fibronectin and collagen type I in normal pancreatic, CP and PC tissues, as well as quiescent/activated PSCs, was investigated...
January 9, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29304760/regulation-of-pancreatic-stellate-cell-activation-by-notch3
#3
Haiyan Song, Yuxiang Zhang
BACKGROUND: Activated pancreatic stellate cells (PaSCs) are the key cellular source of cancer-associated fibroblasts in the pancreatic stroma of patients with pancreatic ductal adenocarcinoma (PDAC), however, the activation mechanism of PaSCs is not yet known. The Notch signaling pathway, components of which are expressed in stromal cells, is involved in the fibrosis of several organs, including the lung and liver. In the current study, we investigated whether Notch signal transduction is involved in PaSC activation in PDAC...
January 5, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29303912/transforming-growth-factor-%C3%AE-and-bone-morphogenetic-protein-2-regulation-of-microrna-200-family-in-chronic-pancreatitis
#4
Peter Yu, Ka Liu, Xuxia Gao, Harry Karmouty-Quintana, Jennifer M Bailey, Yanna Cao, Tien C Ko
OBJECTIVES: To investigate regulation of microRNA (miR)-200 family (a, b, c, 141, and 429) in chronic pancreatitis (CP). This was accomplished by examining miR-200 family levels in a mouse model in vivo and their regulation in pancreatic cells in vitro. METHODS: Chronic pancreatitis was induced by cerulein for 4 weeks (50 μg/kg, 5 hourly intraperitoneal injections/day, and 3 days/week). Control mice received normal saline. The pancreata were harvested for fibrosis assessment by Sirius red staining and for miRNA, collagen, and fibronectin levels by quantitative PCR...
January 5, 2018: Pancreas
https://www.readbyqxmd.com/read/29295482/lipid-metabolism-and-lipid-droplets-in-pancreatic-cancer-and-stellate-cells
#5
REVIEW
Yoshiaki Sunami, Artur Rebelo, Jörg Kleeff
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second deadliest cancer by 2030, and the overall 5-year survival rate is currently less than 7%. Cancer cells frequently exhibit reprogramming of their metabolic activity. It is increasingly recognized that aberrant de novo lipid synthesis and reprogrammed lipid metabolism are both associated with the development and progression of various cancers, including pancreatic cancer. In this review, the current knowledge about lipid metabolism and lipid droplets in pancreatic cancer is discussed...
December 23, 2017: Cancers
https://www.readbyqxmd.com/read/29290790/changes-in-the-microarchitecture-of-the-pancreatic-cancer-stroma-are-linked-to-neutrophil-dependent-reprogramming-of-stellate-cells-and-reflected-by-diffusion-weighted-magnetic-resonance-imaging
#6
Philipp Mayer, Christine Dinkic, Ralf Jesenofsky, Miriam Klauss, Peter Schirmacher, Ulrike Dapunt, Thilo Hackert, Florian Uhle, G Maria Hänsch, Matthias M Gaida
In pancreatic cancer (PDAC) intratumor infiltration of polymorphonuclear neutrophils (PMN) is associated with histologically apparent alterations of the tumor growth pattern. The aim of this study was to examine possible associations between PMN infiltration, tumor microarchitecture, and water diffusivity in diffusion-weighted magnetic resonance imaging (DW-MRI), and to further asses the underlying mechanisms. Methods: DW-MRI was performed in 33 PDAC patients prior to surgery. In parallel, tissue specimen were examined histologically for growth pattern, azurocidin-positive PMN infiltrates, and the presence of alpha-smooth muscle actin (α-SMA) and metalloproteinase 9 (MMP9)-positive myofibroblastic cells...
2018: Theranostics
https://www.readbyqxmd.com/read/29274868/galectin-3-mediates-tumor-cell-stroma-interactions-by-activating-pancreatic-stellate-cells-to-produce-cytokines-via-integrin-signaling
#7
Wei Zhao, Jaffer A Ajani, Guha Sushovan, N Ochi, Rosa Hwang, Margarete Hafley, Randy L Johnson, Robert S Bresalier, Craig D Logsdon, Zhiqian Zhang, Shumei Song
BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is characterized by activated pancreatic stellate cells (PSCs), abundance of extracellular matrix (ECM), and production of cytokines and chemokines. Galectin 3 (GAL3), a β galactoside-specific lectin, contributes to PDAC development but its effects on the stroma and cytokine production are unclear. METHODS: The effect of recombinant human GAL3 (rGAL3) on activation of PSC, production of cytokines, and ECM proteins were determined by proliferation, invasion, cytokine array, and quantitative PCR...
December 21, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29248440/jtc801-induces-ph-dependent-death-specifically-in-cancer-cells-and-slows-growth-of-tumors-in-mice
#8
Xinxin Song, Shan Zhu, Yangchun Xie, Jiao Liu, Lingyi Sun, Dexing Zeng, Pengcheng Wang, Xiaochao Ma, Guido Kroemer, David L Bartlett, Timothy R Billiar, Michael Lotze, Herbert Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Maintenance of acid-base homeostasis is required for normal physiology, metabolism, and development. It is not clear how cell death is activated in response to changes in pH. We performed a screen to identify agents that induce cell death in a pH-dependent manner (we call this alkaliptosis) in pancreatic ductal adenocarcinoma cancer (PDAC) cells and tested their effects in mice. METHODS: We screened a library of 254 compounds that interact with G protein-coupled receptors (GPCRs) to identify those with cytotoxic activity against a human PDAC cell line (PANC1)...
December 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29211796/reprogramming-pancreatic-stellate-cells-via-p53-activation-a-putative-target-for-pancreatic-cancer-therapy
#9
Maya Saison-Ridinger, Kathleen E DelGiorno, Tejia Zhang, Annabelle Kraus, Randall French, Dawn Jaquish, Crystal Tsui, Galina Erikson, Benjamin T Spike, Maxim N Shokhirev, Christopher Liddle, Ruth T Yu, Michael Downes, Ronald M Evans, Alan Saghatelian, Andrew M Lowy, Geoffrey M Wahl
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely dense fibrotic stroma, which contributes to tumor growth, metastasis, and drug resistance. During tumorigenesis, quiescent pancreatic stellate cells (PSCs) are activated and become major contributors to fibrosis, by increasing growth factor signaling and extracellular matrix deposition. The p53 tumor suppressor is known to restrict tumor initiation and progression through cell autonomous mechanisms including apoptosis, cell cycle arrest, and senescence...
2017: PloS One
https://www.readbyqxmd.com/read/29190916/coenzyme-q10-inhibits-the-activation-of-pancreatic-stellate-cells-through-pi3k-akt-mtor-signaling-pathway
#10
Ran Xue, Jing Yang, Jing Wu, Qinghua Meng, Jianyu Hao
Aim: Pancreatic stellate cells (PSCs) have a vital role in pancreatic fibrosis accompanied by pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). Any agents which can affect the activation of PSCs could become potential candidates for treatment strategies in PDAC and CP. Our aim was to explore the effect of Coenzyme Q10 (CoQ10) in the process of PSCs activation. Methods: Isolated PSCs from C57BL/6 mice were treated with various dosages of CoQ10 (1, 10, and 100μM) and different time (24h, 48h, and 72 h)...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163770/role-of-microenvironmental-periostin-in-pancreatic-cancer-progression
#11
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...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156810/psc-derived-galectin-1-inducing-epithelial-mesenchymal-transition-of-pancreatic-ductal-adenocarcinoma-cells-by-activating-the-nf-%C3%AE%C2%BAb-pathway
#12
Dong Tang, Jingqiu Zhang, Zhongxu Yuan, Hongpeng Zhang, Yang Chong, Yuqin Huang, Jie Wang, Qingquan Xiong, Sen Wang, Qi Wu, Ying Tian, Yongdie Lu, Xiao Ge, Wenjing Shen, Daorong Wang
Galectin-1 has previously been shown to be strongly expressed in activated pancreatic stellate cells (PSCs) and promote the development and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the molecular mechanisms by which Galectin-1 promotes the malignant behavior of pancreatic cancer cells remain unclear. In this study, we examined the effects of Galectin-1 knockdown or overexpression in PSCs co-cultured with pancreatic cancer (PANC-1) cells. Immunohistochemical analysis showed expression of epithelial-mesenchymal transition (EMT) markers and MMP9 were positively associated with the expression of Galectin-1 in 66 human PDAC tissues...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155423/experimental-models-of-pancreatic-cancer-desmoplasia
#13
Sujit Suklabaidya, Pujarini Dash, Biswajit Das, Voddu Suresh, Prakash K Sasmal, Shantibhusan Senapati
Desmoplasia is a fibro-inflammatory process and a well-established feature of pancreatic cancer. A key contributor to pancreatic cancer desmoplasia is the pancreatic stellate cell. Various in vitro and in vivo methods have emerged for the isolation, characterization, and use of pancreatic stellate cells in models of cancer-associated fibrosis. In addition to cell culture models, genetically engineered animal models have been established that spontaneously develop pancreatic cancer with desmoplasia. These animal models are currently being used for the study of pancreatic cancer pathogenesis and for evaluating therapeutics against pancreatic cancer...
November 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29152519/primary-carcinosarcoma-of-the-pancreas-with-cd10-positive-sarcoma-component
#14
Christine J Salibay, Julia Rewerska, Shweta Gupta, Nicholas Ree
Carcinosarcomas of the pancreas are rare entities with a dismal prognosis. We report a rare case of pancreatic carcinosarcoma in a 49-year-old African American female who underwent a total abdominal hysterectomy with right salpingo-oophorectomy and exploration of the pancreatic mass. The surgery revealed a sclerotic mass in the body and tail of the pancreas that was surgically unresectable, and a pancreatic biopsy confirmed the pathology of pancreatic carcinosarcoma. Histologically, the lesion showed a high-grade spindle cell sarcoma and adjacent moderately differentiated adenocarcinoma...
October 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/29148265/resveratrol-ameliorates-the-severity-of-fibrogenesis-in-mice-with-experimental-chronic-pancreatitis
#15
Yixuan Xia, Hai-Tao Xiao, Kanglun Liu, Hong-Jie Zhang, Siu Wai Tsang
SCOPE: Resveratrol is generally considered beneficial to health-span and longevity since this dietary stilbenoid has been scrutinized for its activating property on the "rescue gene" sirtuin-1 that promotes cellular survival under stress. In addition to its antiaging property, our previous in vitro studies revealed that resveratrol notably inhibited the production of extracellular matrix (ECM) proteins in pancreatic stellate cells (PSCs), the classic effector cells against pancreatic injury...
November 16, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29129515/amygdalin-improves-microcirculatory-disturbance-and-attenuates-pancreatic-fibrosis-by-regulating-the-expression-of-endothelin-1-and-calcitonin-gene-related-peptide-in-rats
#16
Xiangqun Zhang, Jiangong Hu, Yuzhen Zhuo, Lihua Cui, Caixia Li, Naiqiang Cui, Shukun Zhang
BACKGROUND: The pathogenesis of chronic pancreatitis (CP) is a complex process of interaction between tissue injury and repair, which involves microcirculatory disturbance. Amygdalin, an effective component extracted from Semen Persicae (a kind of Chinese herbal medicine), can decrease blood viscosity and improve microcirculation. In this study, we investigated the therapeutic effects of amygdalin on pancreatic fibrosis in rats with CP. METHODS: The rat CP model was induced by injecting dibutyltin dichloride (DBTC) into the right caudal vein...
November 9, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/29121396/role-of-gut-derived-endotoxin-on-type-i-collagen-production-in-the-rat-pancreas-after-chronic-alcohol-exposure
#17
Hongyan Li, Ming Xiu, Shuhua Wang, David R Brigstock, Li Sun, Limei Qu, Runping Gao
BACKGROUND: Pancreatic fibrosis is a key pathological feature of alcoholic chronic pancreatitis (ACP). Bacterial endotoxin lipopolysaccharide (LPS) is considered as an important cofactor in the fibrogenesis of ACP. However, there are limitations in the use of exogenous LPS for evaluating the role of endotoxin in ACP pathogenesis. In this study we determined the relationship between the concentration of LPS in the portal vein and pancreatic type I collagen (Col1) content in chronic alcohol-fed rats...
November 9, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29111329/exosomes-derived-from-pancreatic-cancer-cells-induce-activation-and-profibrogenic-activities-in-pancreatic-stellate-cells
#18
Atsushi Masamune, Naoki Yoshida, Shin Hamada, Tetsuya Takikawa, Tatsuhide Nabeshima, Tooru Shimosegawa
Pancreatic cancer cells (PCCs) interact with pancreatic stellate cells (PSCs), which play a pivotal role in pancreatic fibrogenesis, to develop the cancer-conditioned tumor microenvironment. Exosomes are membrane-enclosed nanovesicles, and have been increasingly recognized as important mediators of cell-to-cell communications. The aim of this study was to clarify the effects of PCC-derived exosomes on cell functions in PSCs. Exosomes were isolated from the conditioned medium of Panc-1 and SUIT-2 PCCs. Human primary PSCs were treated with PCC-derived exosomes...
October 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29100344/targeting-the-hgf-c-met-pathway-stromal-remodelling-in-pancreatic-cancer
#19
Srinivasa P Pothula, Zhihong Xu, David Goldstein, Neil Merrett, Romano C Pirola, Jeremy S Wilson, Minoti V Apte
Stromal-tumor interactions in pancreatic cancer (PC) impact on treatment outcomes. Pancreatic stellate cells (PSCs) produce the collagenous stroma of PC and interact with cancer cells to facilitate disease progression. A candidate growth factor pathway that may mediate this interaction is the hepatocyte growth factor (HGF)/c-MET pathway. HGF is produced by PSCs and its receptor c-MET is expressed on pancreatic cancer cells. We studied the effects on PC progression of inhibiting the HGF/c-MET pathway in the presence and absence of a representative chemotherapeutic agent, gemcitabine...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29092903/gpr68-a-proton-sensing-gpcr-mediates-interaction-of-cancer-associated-fibroblasts-and-cancer-cells
#20
Shu Z Wiley, Krishna Sriram, Wenjing Liang, Sarah E Chang, Randall French, Thalia McCann, Jason Sicklick, Hiroshi Nishihara, Andrew M Lowy, Paul A Insel
The microenvironment of pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense fibrotic stroma (desmoplasia) generated by pancreatic cancer-associated fibroblasts (CAFs) derived from pancreatic stellate cells (PSCs) and pancreatic fibroblasts (PFs). Using an unbiased GPCRomic array approach, we identified 82 G-protein-coupled receptors (GPCRs) commonly expressed by CAFs derived from 5 primary PDAC tumors. Compared with PSCs and PFs, CAFs have increased expression of GPR68 (a proton-sensing GPCR), with the results confirmed by immunoblotting, The Cancer Genome Atlas data, and immunohistochemistry of PDAC tumors...
November 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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