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pancreatic cancer PSCs

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https://www.readbyqxmd.com/read/29111329/exosomes-derived-from-pancreatic-cancer-cells-induce-activation-and-profibrogenic-activities-in-pancreatic-stellate-cells
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/29069737/functional-heterogeneity-in-tumor-derived-human-pancreatic-stellate-cells-differential-expression-of-hgf-and-implications-for-mitogenic-signaling-and-migration-in-pancreatic-cancer-cells
#4
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...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29061505/pancreatic-stellate-cells-reorganize-matrix-components-and-lead-pancreatic-cancer-invasion-via-the-function-of-endo180
#5
Kazuhiro Koikawa, Kenoki Ohuchida, Shin Takesue, Yohei Ando, Shin Kibe, Hiromichi Nakayama, Sho Endo, Toshiya Abe, Takashi Okumura, Kohei Horioka, Masafumi Sada, Chika Iwamoto, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Riichi Ohuchida, Tatsuya Manabe, Takao Ohtsuka, Eishi Nagai, Kazuhiro Mizumoto, Makoto Hashizume, Masafumi Nakamura
Specific cell populations leading the local invasion of cancer are called "leading cells". However, the underlying mechanisms are unclear. Here, we identified leading cells in pancreatic cancer and determined how these cells lead and promote cancer cell invasion in the extracellular matrix (ECM). Using three-dimensional matrix remodeling assay, we found that pancreatic stellate cells (PSCs) frequently invaded the collagen matrix with pancreatic cancer cells (PCCs), which invaded behind the invading PSCs. In addition, invading PSCs changed the alignment of collagen fibers, resulting in ECM remodeling and an increase in the parallel fibers along the direction of invading PSCs...
October 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28991878/fatty-acid-mediated-stromal-reprogramming-of-pancreatic-stellate-cells-induces-inflammation-and-fibrosis-that-fuels-pancreatic-cancer
#6
Tomoki Hata, Koichi Kawamoto, Hidetoshi Eguchi, Yoshihiro Kamada, Shinji Takamatsu, Tomohiro Maekawa, Satoshi Nagaoka, Daisaku Yamada, Yoshifumi Iwagami, Tadafumi Asaoka, Takehiro Noda, Hiroshi Wada, Kunihito Gotoh, Atsushi Masamune, Eiji Miyoshi, Masaki Mori, Yuichiro Doki
OBJECTIVES: Pancreatic ductal adenocarcinoma is one of the deadliest diseases worldwide. Fatty acids (FAs) have properties that affect both cancer cells and tumor environment. We assessed the effects of FAs on malignant characteristics in a pancreatic cancer and pancreatic stellate cell (PSC) coculture model. This study aimed to clarify the FA signature of PSC-derived inflammation and fibrosis in vitro and in a clinicopathological analysis. METHODS: The in vitro model involved coculture of the human pancreatic cancer cell lines PANC-1 and MIA PaCa-2 with human PSCs...
November 2017: Pancreas
https://www.readbyqxmd.com/read/28837958/terminating-the-criminal-collaboration-in-pancreatic-cancer-nanoparticle-based-synergistic-therapy-for-overcoming-fibroblast-induced-drug-resistance
#7
Liying Wang, Xiangrui Liu, Quan Zhou, Meihua Sui, Zipeng Lu, Zhuxian Zhou, Jianbin Tang, Yi Miao, Min Zheng, Weilin Wang, Youqing Shen
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a dismal overall prognosis mainly unchanged over the past decades. PDAC is generally refractory to conventional treatments, and thus novel therapies are urgently needed. Recently, accumulating evidence has indicated that human pancreatic stellate cells (PSCs) facilitate PDAC development and drug resistance through paracrine activation of hedgehog pathway. Here, we report that smart SN38 (active metabolite of irinotecan) polymeric prodrug-based nanoparticles effectively encapsulate the commercial hedgehog pathway inhibitor GDC-0449 for co-delivery...
August 2, 2017: Biomaterials
https://www.readbyqxmd.com/read/28806504/designing-liposomes-to-suppress-extracellular-matrix-expression-to-enhance-drug-penetration-and-pancreatic-tumor-therapy
#8
Tianjiao Ji, Jiayan Lang, Jing Wang, Rong Cai, Yinlong Zhang, Feifei Qi, Lijing Zhang, Xiao Zhao, Wenjing Wu, Jihui Hao, Zhihai Qin, Ying Zhao, Guangjun Nie
During pancreatic tumor development, pancreatic stellate cells (PSCs) proliferate exuberantly to secrete extracellular matrix (ECM) in the tumor stroma, which presents major barriers for drug delivery and penetration in tumor tissue. Thus, down-regulating ECM levels via regulation of the PSCs may allow enhanced penetration of therapeutic drugs and thereby enhancing their therapeutic efficacy. To regulate the PSCs, a matrix metalloproteinase-2 (MMP-2) responsive peptide-hybrid liposome (MRPL) was constructed via coassembly of a tailor-designed MMP-2 responsive amphiphilic peptide and phospholipids...
September 26, 2017: ACS Nano
https://www.readbyqxmd.com/read/28696100/thermosensitive-liposomal-codelivery-of-hsa-paclitaxel-and-hsa-ellagic-acid-complexes-for-enhanced-drug-perfusion-and-efficacy-against-pancreatic-cancer
#9
Yan Wei, Yuxi Wang, Dengning Xia, Shiyan Guo, Feng Wang, Xinxin Zhang, Yong Gan
Fibrotic stroma and tumor-promoting pancreatic stellate cells (PSCs), critical characters in the pancreatic ductal adenocarcinoma (PDA) microenvironment, promote a tumor-facilitating environment that simultaneously prevents drug penetration into tumor foci and stimulates tumor growth. Nab-PTX, a human serum albumin (HSA) nanoparticle of paclitaxel (PTX), indicates enhanced matrix penetration in PDA probably due to its small size in vivo and high affinity of HSA with secreted protein acidic and rich in cysteine (SPARC), overexpressed in the PDA stroma...
July 24, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28590306/pancreatic-stellate-cells-what-s-new
#10
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...
September 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/28552244/ca-2-signalling-underlying-pancreatitis
#11
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/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
#12
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
#13
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...
October 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
#14
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/28400334/asporin-promotes-pancreatic-cancer-cell-invasion-and-migration-by-regulating-the-epithelial-to-mesenchymal-transition-emt-through-both-autocrine-and-paracrine-mechanisms
#15
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
#16
REVIEW
Tony C Y Pang, Zhihong Xu, Srinivasa Pothula, Therese Becker, David Goldstein, Romano C Pirola, Jeremy S Wilson, Minoti V Apte
Pancreatic stellate cells (PSCs) are 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...
June 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28336327/galectin-1-driven-upregulation-of-sdf-1-in-pancreatic-stellate-cells-promotes-pancreatic-cancer-metastasis
#17
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...
July 1, 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
#18
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...
July 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28217371/pathogenic-mechanisms-of-pancreatitis
#19
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
#20
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
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