Pro-inflammatory cytokine-induced matrix metalloproteinase-1 (MMP-1) secretion in human pancreatic periacinar myofibroblasts

Tasaki, Kazuhito; Shintani, Yutaka; Saotome, Takao; Andoh, Akira; Fujiyama, Yoshihide; Hozawa, Shigenari; Bamba, Tadao

doi:10.1159/000073889

Cited by 28 publications

(20 citation statements)

References 31 publications

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“…While IL-1␤ can directly affect the survival and proliferation of endothelial cells, it can also promote induction of other proangiogenic factors such as TNF␣, angiopoietin-1, IL-6, and VEGF A (Voronov et al 2003;Fan et al 2004;Alagappan et al 2005;Stocks et al 2005). It is especially interesting that IL-1␤ is a potent inducer and activator of matrix metalloproteinases (Wong et al 2001;Tasaki et al 2003;Choi et al 2004), given the ascribed role for MMP9 in triggering VEGF release during the angiogenic switch in RIP-Tag mice (Bergers et al 2000) and the dramatic and rapid release of ECM-bound VEGF we see in islets following Myc activation. Indeed, our own studies indicate that inhibiting MMP activity in isolated pInsMycER TAM ;RIP7-Bcl-x L islets in vitro with the MMP inhibitor GM6001 significantly reduces release of VEGF following Myc activation (K. Shchors and G. Evan, unpubl.…”

Section: Discussionmentioning

confidence: 99%

The Myc-dependent angiogenic switch in tumors is mediated by interleukin 1β

Shchors¹,

Shchors²,

Rostker³

et al. 2006

Genes Dev.

174

142

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Although induction of blood vessel growth is acknowledged as a pivotal requirement for the evolution of macroscopic tumors, the events that trigger onset of tumor angiogenesis remain largely obscure. The pervasive Myc oncoprotein is itself a potent inducer of angiogenesis in a wide range of tissues. We have used a reversibly switchable mouse transgenic model of Myc-dependent ␤-cell carcinogenesis to delineate the kinetics and causal sequence of angiogenic processes following acute Myc activation. We show that onset of endothelial cell proliferation is induced shortly after Myc-induced cell cycle entry of ␤ cells. Endothelial cell proliferation is not indirectly induced by local tissue hypoxia but instead via a diffusible angiogenic signal produced by Myc-expressing ␤ cells. This signal triggers the release of pre-existing, sequestered VEGF from the islet extracellular matrix, that then homes to the endothelial compartment where it induces endothelial cell proliferation. Myc activation in ␤ cells rapidly induces expression and release of the proinflammatory cytokine interleukin 1␤ (IL-1␤). We show that IL-1␤ is the principal effector downstream of Myc responsible for triggering rapid onset of islet angiogenesis. Together, our data delineate a complete pathway in vivo by which the highly pleiotropic Myc oncoproteins elicits coexpansion of the vascular compartment during tumorigenic progression. Induction of blood vessel growth is a pivotal requirement for the evolution of macroscopic tumors. However, the precise molecular mechanisms that trigger angiogenesis in tumors remains largely obscure. Some initial studies in experimental tumor models supported the notion that early tumors are innately incompetent for angiogenesis and, consequently, restricted in size by hypoxia and nutrient privation. The capacity for angiogenesis then arises sporadically during the course of tumor evolution, presumably through the aleatory acquisition of proangiogenic mutations. Recently, however, several studies have indicated that pervasive dominant oncogenes such as Myc and Ras can directly instruct angiogenesis in tissues in which they are activated (Watnick et al. 2003;Knies-Bamforth et al. 2004). Since oncogene activation is likely to be an early and obligate event in tumorigenesis, this intimates that angiogenesis can be an inherent attribute of many tumors from the outset. Deregulated expression of the basic helix-loop-helixleucine zipper (bHLH-LZ) transcription factor Myc is frequent in human cancers. Myc is a pivotal coordinator of a large number of diverse transcriptional programs that coordinate the cellular processes of growth, metabolism, proliferation, and intrinsic tumor suppression. In addition, Myc also regulates various processes by which proliferating cells communicate with, and instruct, appropriate changes in surrounding tissues and stroma, including angiogenesis, invasion, and tissue organization. In this way, Myc integrates intracellular processes required for cell expansion with requisite changes in the local soma...

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Section: Discussionmentioning

confidence: 99%

The Myc-dependent angiogenic switch in tumors is mediated by interleukin 1β

Shchors¹,

Shchors²,

Rostker³

et al. 2006

Genes Dev.

174

142

View full text Add to dashboard Cite

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“…San Francisco Bay Area study show that an increasing number of years between the diagnosis of pancreatitis and pancreatic cancer is associated with a decreasing trend in ORs for pancreatitic cancer (trend P < 0.0001), suggesting that some pancreatitis is more likely to be an early manifestation of pancreatic cancer. 6 TNF-A expression has been associated with the severity of acute pancreatitis (7) and may play a role in tissue remodeling following chronic pancreatitis (8). However, studies of the TNF-A À308 polymorphism and pancreatitis or pancreatic cancer generally have indicated a lack of association (32,33).…”

Section: Discussionmentioning

confidence: 99%

“…Most pancreatic tumors are characterized by intense desmoplasia (5), and there is evidence that proinflammatory cytokines, chemokines, and their receptors are expressed in pancreatic cells and infiltrating immune cells within inflamed pancreatic tissues (6). A number of studies have implicated these molecules as playing a role in pancreatitis progression and tumor development (3,(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Inflammation, Genetic Polymorphisms in Proinflammatory Genes TNF-A, RANTES, and CCR5, and Risk of Pancreatic Adenocarcinoma

Duell

Casella

Burk

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

101

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Adenocarcinoma of the exocrine pancreas is the fourth leading cause of cancer-related death in men and women in the U.S. Cytokines and other proinflammatory mediators have been implicated in inflammatory pancreatic diseases including pancreatitis and cancer. We analyzed cytokine gene polymorphisms as risk factors for pancreatic cancer using questionnaire data obtained by in-person interviews and germ line DNA collected in a population-based case-control study of pancreatic cancer (532 cases and 1,701 controls) conducted in the San Francisco Bay Area. We used mass spectrometry and gel-based methods to genotype 308 cases and 964 population-based controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression analysis and included adjustment for age, sex, and smoking. We assessed potential interactions between these polymorphisms, proinflammatory conditions (e.g., pancreatitis, ulcer, and obesity), and smoking as risk factors for pancreatic cancer. There was no overall association between pancreatic cancer risk and tumor necrosis factor-A (TNF-A À308G/A), regulated upon activation, normally T cellexpressed, and presumably secreted (RANTES À403G/A), and CC chemokine receptor 5 (CCR5-D32) polymorphisms. There was a nearly 7-fold increased relative risk estimate for pancreatic cancer in individuals with a history of pancreatitis (adjusted OR, 6.9; 95% CI, 3.4-14.1). Among patients with pancreatic cancer, pancreatitis was significantly associated with TNF-A À308 GA + AA (OR, 3.1; 95% CI, 1.3-7.4) and with RANTES À403 GA + AA (OR, 2.3; 95% CI, 1.0-5.4). There was evidence for a possible interaction between current active smoking and CCR5-32del. Our results lend support for the hypothesis that proinflammatory gene polymorphisms, in combination with proinflammatory conditions, may influence the development of pancreatic cancer.

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“…Another PSCs function regulated by ERK is MMP-1 production. It has been shown that IL-1b and TNF-a induced MMP-1 production through the activation of ERK, but not NF-jB or p38 MAP kinase [63].…”

Section: Map Kinasesmentioning

confidence: 99%