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Pancreatic Neoplasms: HELP
Articles by Jeremy S. Wilson
Based on 16 articles published since 2009
(Why 16 articles?)
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Between 2009 and 2019, J. S. Wilson wrote the following 16 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Pancreatic stellate cells: what's new? 2017

Pang, Tony C Y / Wilson, Jeremy S / Apte, Minoti V. ·aPancreatic Research Group, South Western Sydney Clinical School, University of New South Wales bIngham Institute for Applied Medical Research, Liverpool, Australia. ·Curr Opin Gastroenterol · Pubmed #28590306.

ABSTRACT: 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. SUMMARY: Traditionally, there have been few treatment options for pancreatitis and pancreatic cancer. The elucidation of the wide-ranging functions of PSCs provide an opportunity for treatments based on stromal reprogramming.

2 Review Circulating pancreatic stellate (stromal) cells in pancreatic cancer-a fertile area for novel research. 2017

Pang, Tony C Y / Xu, Zhihong / Pothula, Srinivasa / Becker, Therese / Goldstein, David / Pirola, Romano C / Wilson, Jeremy S / Apte, Minoti V. ·Pancreatic Research Group, South Western Sydney Clinical School,University of New South Wales, and Ingham Institute of Applied Medical Research, Australia and. · Centre for Circulating Tumour Cell Diagnostics and Research, InghamInstitute for Applied Medical Research, South Western Sydney Clinical School, University of New South Wales, and School ofMedicine, Western Sydney University, Australia. ·Carcinogenesis · Pubmed #28379317.

ABSTRACT: 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.

3 Review Key role of pancreatic stellate cells in pancreatic cancer. 2016

Pothula, Srinivasa P / Xu, Zhihong / Goldstein, David / Pirola, Romano C / Wilson, Jeremy S / Apte, Minoti V. ·Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia; Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia. · Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia. · Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia; Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia. Electronic address: m.apte@unsw.edu.au. ·Cancer Lett · Pubmed #26571462.

ABSTRACT: Pancreatic stellate cells (PSCs) are responsible for producing the collagenous stroma in pancreatic cancer. Findings from the majority of in vitro and in vivo studies to date indicate that PSCs interact with cancer cells as well as with other cellular elements in the stroma including immune cells, endothelial cells and neuronal cells to set up a growth permissive microenvironment for pancreatic tumours. However, two recent studies reporting a protective effect of myofibroblasts in pancreatic cancer have served to remind researchers of the possibility that the role of PSCs in this disease may be context and time-dependent, such that any possible early protective role of PSCs is subverted in later stages by the ability of cancer cells to turn PSCs into cancer-promoting aides. This concept is supported by the development in recent years of several novel therapeutic approaches targeting the stroma that have been successfully applied in pre-clinical settings to inhibit disease progression. A multi-pronged approach aimed at tumour cells as well as stromal elements may be the key to achieving better clinical outcomes in patients with pancreatic cancer.

4 Review Pancreatic stellate cell: physiologic role, role in fibrosis and cancer. 2015

Apte, Minote / Pirola, Romano C / Wilson, Jeremy S. ·Pancreatic Research Group, South Western Sydney Clinical School, University of New South Wales, and Ingham Institute for Applied Medical Research, Sydney, New South Wales, Australia. ·Curr Opin Gastroenterol · Pubmed #26125317.

ABSTRACT: PURPOSE OF REVIEW: Ever since the first descriptions of methods to isolate pancreatic stellate cells (PSCs) from rodent and human pancreas 17 years ago, rapid advances have been made in our understanding of the biology of these cells and their functions in health and disease. This review updates recent literature in the field, which indicates an increasingly complex role for the cells in normal pancreas, pancreatitis and pancreatic cancer. RECENT FINDINGS: Work reported over the past 12 months includes improved methods of PSC immortalization, a role for PSCs in islet fibrosis, novel factors causing PSC activation as well as those inducing quiescence, and translational research aimed at inhibiting the facilitatory effects of PSCs on disease progression in chronic pancreatitis as well as pancreatic cancer. SUMMARY: Improved understanding of the role of PSCs in pancreatic pathophysiology has prompted a focus on translational studies aimed at developing novel approaches to modulate PSC function in a bid to improve clinical outcomes of two major fibrotic diseases of the pancreas: chronic pancreatitis and pancreatic cancer.

5 Review Pancreatic cancer: The microenvironment needs attention too! 2015

Apte, M V / Xu, Z / Pothula, S / Goldstein, D / Pirola, R C / Wilson, J S. ·Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia; Ingham Institute for Applied Medical Research, Sydney, Australia. Electronic address: m.apte@unsw.edu.au. · Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia; Ingham Institute for Applied Medical Research, Sydney, Australia. · Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia; Department of Medical Oncology, Prince of Wales Hospital, Sydney, and Faculty of Medicine, University of New South Wales, Sydney, Australia. ·Pancreatology · Pubmed #25845856.

ABSTRACT: The abundant stromal/desmoplastic reaction, a characteristic feature of a majority of pancreatic adenocarcinomas (PDAC), has only recently been receiving some attention regarding its possible role in the pathobiology of pancreatic cancer. It is now well established that the cells predominantly responsible for producing the collagenous stroma are pancreatic stellate cells (PSCs). In addition to extracellular matrix proteins, the stroma also exhibits cellular elements including, immune cells, endothelial cells and neural cells. Evidence is accumulating to indicate the presence of significant interactions between PSCs and cancer cells as well as between PSCs and other cell types in the stroma. The majority of research reports to date, using in vitro and in vivo approaches, suggest that these interactions facilitate local growth as well as distant metastasis of pancreatic cancer, although a recent study using animals depleted of myofibroblasts has raised some questions regarding the central role of myofibroblasts in cancer progression. Nonetheless, novel therapeutic strategies have been assessed, mainly in the pre-clinical setting, in a bid to interrupt stromal-tumour interactions and inhibit disease progression. The next important challenge is for the translation of such pre-clinical strategies to the clinical situation so as to improve the outcome of patients with pancreatic cancer.

6 Review Pancreatic cancer and its stroma: a conspiracy theory. 2014

Xu, Zhihong / Pothula, Srinivasa P / Wilson, Jeremy S / Apte, Minoti V. ·Zhihong Xu, Srinivasa P Pothula, Jeremy S Wilson, Minoti V Apte, Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, NSW 2170, Australia. ·World J Gastroenterol · Pubmed #25170206.

ABSTRACT: Pancreatic cancer is characterised by a prominent desmoplastic/stromal reaction that has received little attention until recent times. Given that treatments focusing on pancreatic cancer cells alone have failed to significantly improve patient outcome over many decades, research efforts have now moved to understanding the pathophysiology of the stromal reaction and its role in cancer progression. In this regard, our Group was the first to identify the cells (pancreatic stellate cells, PSCs) that produced the collagenous stroma of pancreatic cancer and to demonstrate that these cells interacted closely with cancer cells to facilitate local tumour growth and distant metastasis. Evidence is accumulating to indicate that stromal PSCs may also mediate angiogenesis, immune evasion and the well known resistance of pancreatic cancer to chemotherapy and radiotherapy. This review will summarise current knowledge regarding the critical role of pancreatic stellate cells and the stroma in pancreatic cancer biology and the therapeutic approaches being developed to target the stroma in a bid to improve the outcome of this devastating disease.

7 Review A starring role for stellate cells in the pancreatic cancer microenvironment. 2013

Apte, Minoti V / Wilson, Jeremy S / Lugea, Aurelia / Pandol, Stephen J. ·Pancreatic Research Groups, University of New South Wales Sydney, New South Wales, Australia. ·Gastroenterology · Pubmed #23622130.

ABSTRACT: Pancreatic ductal adenocarcinoma is a devastating disease, and patient outcomes have not improved in decades. Treatments that target tumor cells have largely failed. This could be because research has focused on cancer cells and the influence of the stroma on tumor progression has been largely ignored. The focus of pancreatic cancer research began to change with the identification of pancreatic stellate cells, which produce the pancreatic tumor stroma. There is compelling in vitro and in vivo evidence for the influence of pancreatic stellate cells on pancreatic cancer development; several recent preclinical studies have reported encouraging results with approaches designed to target pancreatic stellate cells and the stroma. We review the background and recent advances in these areas, along with important areas of future research that could improve therapy.

8 Review The burning question: why is smoking a risk factor for pancreatic cancer? 2012

Pandol, Stephen J / Apte, Minoti V / Wilson, Jeremy S / Gukovskaya, Anna S / Edderkaoui, Mouad. ·Veterans Affairs Greater Los Angeles Healthcare System, University of California Los Angeles, CA 90073, USA. ·Pancreatology · Pubmed #22898636.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease. The prognosis is poor; less than 5% of those diagnosed are still alive five years after diagnosis, and complete remission is still rare. Tobacco smoking is a major risk factor of pancreatic cancer. However, the mechanism(s) through which it causes the disease remains unknown. Accumulating evidence indicates that carcinogenic compounds in cigarette smoke stimulate pancreatic cancer progression through induction of inflammation and fibrosis which act in concert with genetic factors leading to the inhibition of cell death and stimulation of proliferation resulting in the promotion of the PDAC.

9 Review Dangerous liaisons: pancreatic stellate cells and pancreatic cancer cells. 2012

Apte, Minoti V / Wilson, Jeremy S. ·Pancreatic Research Group, South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia. m.apte@unsw.edu.au ·J Gastroenterol Hepatol · Pubmed #22320920.

ABSTRACT: One of the characteristic features of the majority of pancreatic ductal adenocarcinomas is an abundant desmoplastic/stromal reaction. Until recently, this stroma had received little attention from researchers studying the pathogenesis of pancreatic cancer, with most of the research focus resting on the biology of tumor cells themselves. However, evidence is now accumulating that the stroma plays a critical role in pancreatic cancer progression. The cells responsible for producing the stromal reaction in pancreatic cancer are activated pancreatic stellate cells (PSCs, the key effector cells in pancreatic fibrogenesis). In vitro and in vivo studies have convincingly demonstrated a close bi-directional interaction between PSCs and pancreatic cancer cells, which facilitates local tumor growth as well as distant metastasis. PSCs also interact closely with endothelial cells to stimulate angiogenesis and are possibly involved in the known resistance of pancreatic cancer to chemotherapy and radiation. Most interestingly, it has recently been shown that PSCs from the primary tumor can travel to distant metastatic sites where they likely facilitate the seeding, survival, and proliferation of cancer cells. Thus, it is now recognized that the stroma is an important alternative therapeutic target in this disease and concerted pre-clinical research is underway to develop strategies to modulate/deplete the stromal reaction to inhibit cancer progression. The challenge is to translate these developments into clinically applicable treatments for patients.

10 Review New insights into alcoholic pancreatitis and pancreatic cancer. 2009

Apte, Minoti / Pirola, Romano / Wilson, Jeremy. ·Pancreatic Research Group, South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia. m.apte@unsw.edu.au ·J Gastroenterol Hepatol · Pubmed #19799699.

ABSTRACT: Pancreatitis and pancreatic cancer represent two major diseases of the exocrine pancreas. Pancreatitis exhibits both acute and chronic manifestations. The commonest causes of acute pancreatitis are gallstones and alcohol abuse; the latter is also the predominant cause of chronic pancreatitis. Recent evidence indicates that endotoxinemia, which occurs in alcoholics due to increased gut permeability, may trigger overt necroinflammation of the pancreas in alcoholics and one that may also play a critical role in progression to chronic pancreatitis (acinar atrophy and fibrosis) via activation of pancreatic stellate cells (PSCs). Chronic pancreatitis is a major risk factor for the development of pancreatic cancer, which is the fourth leading cause of cancer-related deaths in humans. Increasing attention has been paid in recent years to the role of the stroma in pancreatic cancer progression. It is now well established that PSCs play a key role in the production of cancer stroma and that they interact closely with cancer cells to create a tumor facilitatory environment that stimulates local tumor growth and distant metastasis. This review summarizes recent advances in our understanding of the pathogenesis of alcoholic pancreatitis and pancreatic cancer, with particular reference to the central role played by PSCs in both diseases. An improved knowledge of PSC biology has the potential to provide an insight into pathways that may be therapeutically targeted to inhibit PSC activation, thereby inhibiting the development of fibrosis in chronic pancreatitis and interrupting stellate cell-cancer cell interactions so as to retard cancer progression.

11 Article Pancreatic cancer: A multipronged approach to pancreatic cancer treatment. 2016

Apte, Minoti V / Wilson, Jeremy S. ·Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, NSW 2170, Australia; and the Ingham Institute for Applied Medical Research, Liverpool Hospital, Liverpool, NSW 2170, Australia. ·Nat Rev Gastroenterol Hepatol · Pubmed #27188822.

ABSTRACT: -- No abstract --

12 Article Hepatocyte growth factor inhibition: a novel therapeutic approach in pancreatic cancer. 2016

Pothula, Srinivasa P / Xu, Zhihong / Goldstein, David / Biankin, Andrew V / Pirola, Romano C / Wilson, Jeremy S / Apte, Minoti V. ·Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia. · Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia. · Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia. · Cancer Research Division, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. ·Br J Cancer · Pubmed #26766740.

ABSTRACT: BACKGROUND: Pancreatic stellate cells (PSCs, which produce the stroma of pancreatic cancer (PC)) interact with cancer cells to facilitate PC growth. A candidate growth factor pathway that may mediate this interaction is the HGF-c-MET pathway. METHODS: Effects of HGF inhibition (using a neutralising antibody AMG102) alone or in combination with gemcitabine were assessed (i) in vivo using an orthotopic model of PC, and (ii) in vitro using cultured PC cells (AsPC-1) and human PSCs. RESULTS: We have shown that human PSCs (hPSCs) secrete HGF but do not express the receptor c-MET, which is present predominantly on cancer cells. HGF inhibition was as effective as standard chemotherapy in inhibiting local tumour growth but was significantly more effective than gemcitabine in reducing tumour angiogenesis and metastasis. HGF inhibition has resulted in reduced metastasis; however, interestingly this antimetastatic effect was lost when combined with gemcitabine. This suggests that gemcitabine treatment selects out a subpopulation of cancer cells with increased epithelial-mesenchymal transition (EMT) and stem-cell characteristics, as supported by our findings of increased expression of EMT and stem-cell markers in tumour sections from our animal model. In vitro studies showed that hPSC secretions induced proliferation and migration, but inhibited apoptosis, of cancer cells. These effects were countered by pretreatment of hPSC secretions with a HGF-neutralising antibody but not by gemcitabine, indicating a key role for HGF in PSC-PC interactions. CONCLUSIONS: Our studies suggest that targeted therapy to inhibit stromal-tumour interactions mediated by the HGF-c-MET pathway may represent a novel therapeutic approach in PC that will require careful modelling for optimal integration with existing treatment modalities.

13 Article Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy. 2014

Sherman, Mara H / Yu, Ruth T / Engle, Dannielle D / Ding, Ning / Atkins, Annette R / Tiriac, Herve / Collisson, Eric A / Connor, Frances / Van Dyke, Terry / Kozlov, Serguei / Martin, Philip / Tseng, Tiffany W / Dawson, David W / Donahue, Timothy R / Masamune, Atsushi / Shimosegawa, Tooru / Apte, Minoti V / Wilson, Jeremy S / Ng, Beverly / Lau, Sue Lynn / Gunton, Jenny E / Wahl, Geoffrey M / Hunter, Tony / Drebin, Jeffrey A / O'Dwyer, Peter J / Liddle, Christopher / Tuveson, David A / Downes, Michael / Evans, Ronald M. ·Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA. · Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. · Department of Medicine/Hematology and Oncology, University of California San Francisco, San Francisco, CA 94143, USA. · Cancer Research UK Cambridge Research Institute, The Li Ka Shing Centre, Robinson Way, Cambridge CB2 ORE, UK. · Center for Advanced Preclinical Research, NCI-Frederick, Frederick, MD 21702, USA. · Center for Advanced Preclinical Research, Leidos Biomed, Inc. Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. · Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai Miyagi, 980-8574, Japan. · Pancreatic Research Group, Faculty of Medicine, South Western Sydney Clinical School, University of New South Wales, Sydney, NSW 2052, Australia. · Diabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, NSW 2052, Australia. · Diabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, NSW 2010, Australia; Faculty of Medicine, University of Sydney, Sydney, NSW 2052, Australia; Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW 2145, Australia. · Diabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, NSW 2052, Australia; Faculty of Medicine, University of Sydney, Sydney, NSW 2052, Australia; Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW 2145, Australia. · Molecular and Cell Biology Laboratory, Salk Institute, La Jolla, CA 92037, USA. · Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA. · Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. · The Storr Liver Unit, Westmead Millennium Institute and University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia. · Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA. Electronic address: downes@salk.edu. · Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA. Electronic address: evans@salk.edu. ·Cell · Pubmed #25259922.

ABSTRACT: The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment. Conversion of quiescent to activated pancreatic stellate cells (PSCs) drives the severe stromal reaction that characterizes PDA. Here, we reveal that the vitamin D receptor (VDR) is expressed in stroma from human pancreatic tumors and that treatment with the VDR ligand calcipotriol markedly reduced markers of inflammation and fibrosis in pancreatitis and human tumor stroma. We show that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone. This work describes a molecular strategy through which transcriptional reprogramming of tumor stroma enables chemotherapeutic response and suggests vitamin D priming as an adjunct in PDA therapy. PAPERFLICK:

14 Article The role of the hepatocyte growth factor/c-MET pathway in pancreatic stellate cell-endothelial cell interactions: antiangiogenic implications in pancreatic cancer. 2014

Patel, Mishaal B / Pothula, Srinivasa P / Xu, Zhihong / Lee, Alexandra K / Goldstein, David / Pirola, Romano C / Apte, Minoti V / Wilson, Jeremy S. ·Pancreatic Research Group, South Western Sydney Clinical School, Ingham Institute for Applied Medical Research and the School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2170, Australia. · Pancreatic Research Group, South Western Sydney Clinical School, Ingham Institute for Applied Medical Research and the School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2170, Australia. m.apte@unsw.edu.au. ·Carcinogenesis · Pubmed #24876152.

ABSTRACT: Activated cancer-associated human pancreatic stellate cells (CAhPSCs, which produce the collagenous stroma of pancreatic cancer [PC]) are known to play a major role in PC progression. Apart from inducing cancer cell proliferation and migration, CAhPSCs have also been implicated in neoangiogenesis in PC. However, the mechanisms mediating the observed angiogenic effects of CAhPSCs are unknown. A candidate pathway that may be involved in this process is the hepatocyte growth factor (HGF)/c-MET pathway and its helper molecule, urokinase-type plasminogen activator (uPA). This study investigated the effects of CAhPSC secretions on endothelial cell function in the presence and absence of HGF, c-MET and uPA inhibitors. HGF levels in CAhPSC secretions were quantified using ELISA. CAhPSC secretions were then incubated with human microvascular endothelial cells (HMEC-1) and angiogenesis assessed by quantifying HMEC-1 tube formation and proliferation. CAhPSC-secreted HGF significantly increased HMEC-1 tube formation and proliferation; notably, these effects were downregulated by inhibition of HGF, its receptor c-MET and uPA. Phosphorylation of p38 mitogen-activated protein kinase was downregulated during inhibition of the HGF/c-MET pathway, whereas phosphatidylinositol-3 kinase and ERK1/2 remained unaffected. Our studies have shown for the first time that CAhPSCs induce proliferation and tube formation of HMEC-1 and that the HGF/c-MET pathway plays a major role in this induction. Given that standard antiangiogenic treatment targeting vascular endothelial growth factor has had limited success in the clinical setting, the findings of the current study provide strong support for a novel, alternative antiangiogenic approach targeting the HGF/c-MET and uPA pathways in PC.

15 Article StellaTUM: current consensus and discussion on pancreatic stellate cell research. 2012

Erkan, Mert / Adler, Guido / Apte, Minoti V / Bachem, Max G / Buchholz, Malte / Detlefsen, Sönke / Esposito, Irene / Friess, Helmut / Gress, Thomas M / Habisch, Hans-Joerg / Hwang, Rosa F / Jaster, Robert / Kleeff, Jörg / Klöppel, Günter / Kordes, Claus / Logsdon, Craig D / Masamune, Atsushi / Michalski, Christoph W / Oh, Junseo / Phillips, Phoebe A / Pinzani, Massimo / Reiser-Erkan, Carolin / Tsukamoto, Hidekazu / Wilson, Jeremy. ·Department of General Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. m.mert.erkan@googlemail.com ·Gut · Pubmed #22115911.

ABSTRACT: -- No abstract --

16 Article Role of pancreatic stellate cells in pancreatic cancer metastasis. 2010

Xu, Zhihong / Vonlaufen, Alain / Phillips, Phoebe A / Fiala-Beer, Eva / Zhang, Xuguo / Yang, Lu / Biankin, Andrew V / Goldstein, David / Pirola, Romano C / Wilson, Jeremy S / Apte, Minoti V. ·Pancreatic Research Group, South Western Sydney Clinical School, School of Medical Sciences, Faculty of Medicine, Room 505, Level 5, Wallace Wurth Building, The University of New South Wales, Sydney, NSW 2052, Australia. ·Am J Pathol · Pubmed #20934972.

ABSTRACT: Pancreatic stellate cells (PSCs) produce the stromal reaction in pancreatic cancer (PC), and their interaction with cancer cells facilitates cancer progression. This study investigated the role of human PSCs (hPSCs) in the metastatic process and tumor angiogenesis using both in vivo (orthotopic model) and in vitro (cultured PSC and PC cells) approaches. A sex mismatch study (injection of male hPSCs plus female PC cells into the pancreas of female mice) was conducted to determine whether hPSCs accompany cancer cells to metastatic sites. Metastatic nodules were examined by fluorescent in situ hybridization for the presence of the Y chromosome. Angiogenesis was assessed by i) immunostaining tumors for CD31, an endothelial cell marker; and ii) quantifying human microvascular endothelial cell (HMEC-1) tube formation in vitro on exposure to conditioned media from hPSCs. Transendothelial migration was assessed in vitro by examining the movement of fluorescently labeled hPSCs through an endothelial cell monolayer. Human PSCs i) were found in multiple metastatic sites in each mouse injected with male hPSCs plus female PC cells; ii) increased CD31 expression in primary tumors from mice injected with MiaPaCa-2 and hPSCs and stimulated tube formation by HMEC-1 in vitro; and iii) exhibited transendothelial migration that was stimulated by cancer cells. Human PSCs accompany cancer cells to metastatic sites, stimulate angiogenesis, and are able to intravasate/extravasate to and from blood vessels.