Interleukin-1β stimulates matrix metalloproteinase-2 expression via a prostaglandin E2-dependent mechanism in human chondrocytes

Choi, Young‐Ae; Lee, Dongjun; Lim, Hyung-Kyu; Jeong, Jaeho; Sonn, Jong-Kyung; Kang, Shin‐Sung; Baek, Suk‐Hwan

doi:10.1038/emm.2004.31

Cited by 23 publications

(17 citation statements)

References 21 publications

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“…This can reduce tumor cell proliferation and invasion. It has also been shown that COX-2 inhibitor significantly reduced tumor-induced MMP-2 and MMP-9 expression in cancer models (21,46). To elucidate the possible link between COX-2/VEGFR and the proteolytic enzymes, cells were treated with SC-236 or CBO-P11 to examine the effects on MMP-2 and MMP-9 as well as uPA and uPAR on gastric cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Nicotine Induces Cyclooxygenase-2 and Vascular Endothelial Growth Factor Receptor-2 in Association with Tumor-Associated Invasion and Angiogenesis in Gastric Cancer

Shin¹,

Wu²,

Chu³

et al. 2005

Molecular Cancer Research

107

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Blockade of angiogenesis is a promising strategy to suppress tumor growth, invasion, and metastasis. Vascular endothelial growth factor (VEGF), which binds to tyrosine kinase receptors [VEGF receptors (VEGFR) 1 and 2], is the mediator of angiogenesis and mitogen for endothelial cells. Cyclooxygenase-2 (COX-2) plays an important role in the promoting action of nicotine on gastric cancer growth. However, the action of nicotine and the relationship between COX-2 and VEGF/VEGFR system in tumorigenesis remain undefined. In this study, the effects of nicotine in tumor angiogenesis, invasiveness, and metastasis were studied with sponge implantation and Matrigel membrane models. Nicotine (200 Mg/mL) stimulated gastric cancer cell proliferation, which was blocked by SC-236 (a highly selective COX-2 inhibitor) and CBO-P11 (a VEGFR inhibitor). This was associated with decreased VEGF levels as well as VEGFR-2 but not VEGFR-1 expression. Topical injection of nicotine enhanced tumor-associated vascularization, with a concomitant increase in VEGF levels in sponge implants. Again, application of SC-236 (2 mg/kg) and CBO-P11 (0.4 mg/kg) partially attenuated vascularization by f30%. Furthermore, nicotine enhanced tumor cell invasion through the Matrigel membrane by 4-fold and promoted migration of human umbilical vein endothelial cells in a cocultured system with gastric cancer cells. The activity of matrix metalloproteinases 2 and 9 and protein expressions of plasminogen activators (urokinase-type plasminogen activator and its receptor), which are the indicators of invasion and migration processes, were increased by nicotine but blocked by COX-2 and VEGFR inhibitors. Taken together, our results reveal that the promoting action of nicotine on angiogenesis, tumor invasion, and metastasis is COX-2/VEGF/VEGFR dependent. (Mol Cancer Res 2005;3(11):607 -15)

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Section: Discussionmentioning

confidence: 99%

Nicotine Induces Cyclooxygenase-2 and Vascular Endothelial Growth Factor Receptor-2 in Association with Tumor-Associated Invasion and Angiogenesis in Gastric Cancer

Shin¹,

Wu²,

Chu³

et al. 2005

Molecular Cancer Research

107

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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.

176

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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“…After induction, COX-2 participates in the sequential enzymatic reactions that lead to the synthesis of PGE2, which, by binding to the EP2 and EP4 PGE2 receptors present in the joint tissues, play a major role in cartilage degradation and OA progression [89]. For example, PGE2 participates in IL-1β-induced MMP-2 expression and activation [90] and induces apoptosis [91] in articular chondrocytes. Moreover, depending on dose and specific redox derivatives, NO can also have negative, as well as positive effects on OA progression, with specific NO derivatives sustaining NF-κB activation in response to pro-inflammatory stimuli and other forms of NO inhibiting its induction (reviewed in [84]).…”

Section: Introductionmentioning

confidence: 99%

NF-κB Signaling: Multiple Angles to Target OA

Marcu¹,

Otero²,

Olivotto³

et al. 2010

CDT

517

427

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In the context of OA disease, NF-κB transcription factors can be triggered by a host of stress-related stimuli including pro-inflammatory cytokines, excessive mechanical stress and ECM degradation products. Activated NF-κB regulates the expression of many cytokines and chemokines, adhesion molecules, inflammatory mediators, and several matrix degrading enzymes. NF-κB also influences the regulated accumulation and remodeling of ECM proteins and has indirect positive effects on downstream regulators of terminal chondrocyte differentiation (including β-catenin and Runx2). Although driven partly by pro-inflammatory and stress-related factors, OA pathogenesis also involves a “loss of maturational arrest” that inappropriately pushes chondrocytes towards a more differentiated, hypertrophic-like state. Growing evidence points to NF-κB signaling as not only playing a central role in the pro-inflammatory stress-related responses of chondrocytes to extra- and intra-cellular insults, but also in the control of their differentiation program. Thus unlike other signaling pathways the NF-κB activating kinases are potential therapeutic OA targets for multiple reasons. Targeted strategies to prevent unwanted NF-κB activation in this context, which do not cause side effects on other proteins or signaling pathways, need to be focused on the use of highly specific drug modalities, siRNAs or other biological inhibitors that are targeted to the activating NF-κB kinases IKKα or IKKβ or specific activating canonical NF-κB subunits. However, work remains in its infancy to evaluate the effects of efficacious, targeted NF-κB inhibitors in animal models of OA disease in vivo and to also target these strategies only to affected cartilage and joints to avoid other undesirable systemic effects.

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Interleukin-1β stimulates matrix metalloproteinase-2 expression via a prostaglandin E2-dependent mechanism in human chondrocytes

Cited by 23 publications

References 21 publications

Nicotine Induces Cyclooxygenase-2 and Vascular Endothelial Growth Factor Receptor-2 in Association with Tumor-Associated Invasion and Angiogenesis in Gastric Cancer

Nicotine Induces Cyclooxygenase-2 and Vascular Endothelial Growth Factor Receptor-2 in Association with Tumor-Associated Invasion and Angiogenesis in Gastric Cancer

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

NF-κB Signaling: Multiple Angles to Target OA

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Interleukin-1β stimulates matrix metalloproteinase-2 expression via a prostaglandin E2-dependent mechanism in human chondrocytes

Cited by 23 publications

References 21 publications

Nicotine Induces Cyclooxygenase-2 and Vascular Endothelial Growth Factor Receptor-2 in Association with Tumor-Associated Invasion and Angiogenesis in Gastric Cancer

Nicotine Induces Cyclooxygenase-2 and Vascular Endothelial Growth Factor Receptor-2 in Association with Tumor-Associated Invasion and Angiogenesis in Gastric Cancer

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

NF-&#954;B Signaling: Multiple Angles to Target OA

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NF-κB Signaling: Multiple Angles to Target OA