Amphiregulin is a potent mitogen for the vascular smooth muscle cell line, A7r5

Kato, Masayuki; Inazu, Toshiyuki; Kawai, Yasuyuki; Masamura, Katsumi; Yoshida, Masahiro; Tanaka, Nobuyoshi; Miyamoto, Kaoru; Miyamori, Isamu

doi:10.1016/s0006-291x(03)00093-7

Cited by 34 publications

(29 citation statements)

References 28 publications

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“…12 Kato et al showed that AREG can induce the proliferation of rat vascular smooth muscle cells and could be implicated in arterial remodeling. 13 We demonstrated here for the first time that human and mouse DCs are a source of AREG, an EGFR ligand with tumorigenic properties. …”

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confidence: 76%

“…13,17 To investigate the functional effect of AREG secreted by MoDCs, HA-VSMCs were incubated with DC supernatants pretreated or not with an anti-AREG blocking antibody ( Figure 1D). Supernatants of DCs treated with the combination of ATP␥S and LPS were used in these experiments because of their high content of AREG.…”

Section: Areg Secreted By Dcs Increases Smooth Muscle Cell Growthmentioning

confidence: 99%

“…13 Interestingly AREG is commonly overexpressed in cancerous tissues such as human colon, stomach, breast, and pancreas, in which the level of AREG is correlated with tumor progression and poor patient survival. [40][41][42] The secretion of AREG by immune cells has been poorly described so far.…”

Section: Tumorigenic Properties Of Atp-treated Dendritic Cells 3223mentioning

confidence: 99%

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ATP confers tumorigenic properties to dendritic cells by inducing amphiregulin secretion

Bles

Pietrantonio

Boeynaems

et al. 2010

Blood

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IntroductionThe interactions between the immune system and angiogenesis are determinant for the regulation of tumor growth. The mechanisms of these interactions are not well understood at this time. Dendritic cells (DCs) are known to play a central role in these interactions by releasing vascular endothelial growth factor-A (VEGF-A). 1,2 VEGF-A is able to induce endothelial-like differentiation of tumor-infiltrating precursors of DCs and their migration to vessels to participate to vasculogenesis. 3 VEGF-A was also reported to inhibit the function of mature DCs. 4 Immune cells such as tumor-associated macrophages and T cells were also reported to regulate angiogenesis through the secretion of potent angiogenic mediators such as angiopoietin-2 and interleukin-17 . 5,6 We demonstrated previously that ATP up-regulates the expression by monocyte-derived DCs (MoDCs) of numerous genes that may play a role in immunosuppression, in particular thrombospondin-1 and indoleamine 2,3-dioxygenase. 2,7 Some epidermal growth factor receptor (EGFR) ligands were also ATP target genes in MoDCs, in particular, amphiregulin (AREG), which was the most highly up-regulated gene. AREG is a cell type-dependent mitogenic factor that binds to ErbB1 receptor, also called EGFR. 8 AREG is implicated in tumorigenesis and angiogenesis. 9,10 Ma et al showed a reduction of the tumor mass and the intratumoral vascularization using an antisense cDNA of AREG in a breast cell line. 11 A clinical study showed that there was a significant overexpression of AREG and VEGF in primary breast cancer. 12 Kato et al showed that AREG can induce the proliferation of rat vascular smooth muscle cells and could be implicated in arterial remodeling. 13 We demonstrated here for the first time that human and mouse DCs are a source of AREG, an EGFR ligand with tumorigenic properties. Methods MiceMale 6-to 8-week-old C57BL/6 mice were obtained from Charles River Laboratories. All animal experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals as adopted and promulgated by the US National Institutes of Health (NIH) and were approved by the Comission d'Ethique et du Bien-Etre Animal (CEBEA) ethical committee. ReagentsATP, adenosine 5Ј-O-(3-thiotriphosphate; ATP␥S), UTP, prostaglandin E2 (PGE 2 ), adenosine (Ado), NECA (5Ј-(N-ethylcarboxamido)adenosine), suramin, MRS1754, and lipopolysaccharide (LPS) were obtained from Sigma-Aldrich. Monoclonal anti-human and anti-mouse AREG blocking antibodies were purchased at R&D Systems. Preparation of human monocyte-derived DCsPeripheral blood mononuclear cells were isolated from leukocyte-enriched buffy coats of healthy volunteer donors by standard density gradient centrifugation using Lymphoprep solution from Nycomed. Mononuclear cells (2.5 ϫ 10 8 ) were allowed to adhere during 1 hour and 30 minutes at 37°C at 5% CO 2 in 75-cm 2 cell culture flasks. Nonadherent cells were removed, and adherent cells were cultured in 15 mL of culture medium For personal use only. on April 4, 2019. by guest ...

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confidence: 76%

Section: Areg Secreted By Dcs Increases Smooth Muscle Cell Growthmentioning

confidence: 99%

Section: Tumorigenic Properties Of Atp-treated Dendritic Cells 3223mentioning

confidence: 99%

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ATP confers tumorigenic properties to dendritic cells by inducing amphiregulin secretion

Bles

Pietrantonio

Boeynaems

et al. 2010

Blood

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“…10 AR shows bifunctional properties, stimulating the proliferation of a variety of normal cells and inhibiting that of many tumor cell lines. 7,9,11 Together these observations prompted us to examine AR gene expression in liver injury and during experimental liver regeneration. We show here that the expression of AR is detected in the liver of cirrhotic patients and is rapidly induced in rodent liver after PH.…”

Section: Background and Aimsmentioning

confidence: 99%

Amphiregulin: An early trigger of liver regeneration in mice

et al. 2005

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See editorial on page 504. Background & Aims:Liver regeneration is a unique response directed to restore liver mass after resection or injury. The survival and proliferative signals triggered during this process are conveyed by a complex network of cytokines and growth factors acting in an orderly manner. Activation of the epidermal growth factor receptor is thought to play an important role in liver regeneration. Amphiregulin is a member of the epidermal growth factor family whose expression is not detectable in healthy liver. We have investigated the expression of amphiregulin in liver injury and its role during liver regeneration after partial hepatectomy. Methods: Amphiregulin gene expression was examined in healthy and cirrhotic human and rat liver, in rodent liver regeneration after partial hepatectomy, and in primary hepatocytes. The proliferative effects and intracellular signaling of amphiregulin were studied in isolated hepatocytes. The in vivo role of amphiregulin in liver regeneration after partial hepatectomy was analyzed in amphiregulin-null mice. Results: Amphiregulin gene expression is detected in chronically injured human and rat liver and is rapidly induced after partial hepatectomy in rodents. Amphiregulin expression is induced in isolated hepatocytes by interleukin 1␤ and prostaglandin E 2 , but not by hepatocyte growth factor, interleukin 6, or tumor necrosis factor ␣. We show that amphiregulin behaves as a primary mitogen for isolated hepatocytes, acting through the epidermal growth factor receptor. Finally, amphiregulin-null mice display impaired proliferative responses after partial liver resection. Conclusions: Our findings indicate that amphiregulin is an earlyresponse growth factor that may contribute to the initial phases of liver regeneration.

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“…The present findings may thus have clinical implications, especially since amphiregulin and transforming growth factora appear significantly released after exposure to only 1 mg?cm -2 of native particulate matter with a diameter ,2.5 mm, a concentration easily reached in the tracheobronchial region of individuals with respiratory diseases living in polluted urban areas [22]. In addition to the role of particulate matter-induced epidermal growth factor receptor ligands in sustained bronchial inflammation, they may also have paracrine effects on other cellular actors involved in airway remodelling, such as fibroblasts or vascular smooth muscle cells previously described to be sensitive to such ligands [29,30].…”

Section: Pm25-induced Egfr Ligands Mediate a Pro-inflammatory Responmentioning

confidence: 99%

Expression and role of EGFR ligands induced in airway cells by PM2.5 and its components

Rumelhard¹,

Ramgolam²,

Hamel³

et al. 2007

European Respiratory Journal

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The aim of the current study was to establish the epidermal growth factor receptor (EGFR) ligand expression profile in human airway epithelial cells exposed to either particulate matter (PM) with an aerodynamic diameter ,2.5 mm (PM2.5) or its components and the involvement of EGFR ligands in PM2.5-provoked airway inflammation.EGFR ligand mRNA and protein expression were studied in a human bronchial epithelial cell line and normal nasal cells exposed to noncytotoxic concentrations of PM2.5 or its components. The autocrine role of EGFR ligands in airway epithelial cell pro-inflammation was determined by adding conditioned media from PM2.5-treated cells to fresh cells and measuring the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF), a pro-inflammatory biomarker.PM2.5 increased amphiregulin, transforming growth factor-a and heparin-binding EGF-like growth factor mRNA expression and protein secretion, with a slight contribution of aqueous metallic compounds and a strong participation of organic components putatively attributed to PM polyaromatic hydrocarbon content. PM2.5-induced EGFR ligands were involved in cellular GM-CSF release.The current study revealed upregulation of several epidermal growth factor receptor ligands by airway epithelial cells exposed to particulate matter with an aerodynamic diameter ,2.5 mm and their contribution to bronchial epithelial cell granulocyte-macrophage colony-stimulating factor secretion by an autocrine action, suggesting that these ligands could elicit and sustain the particulate matter-induced airway pro-inflammatory response and contribute to bronchial remodelling.

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Amphiregulin is a potent mitogen for the vascular smooth muscle cell line, A7r5

Cited by 34 publications

References 28 publications

ATP confers tumorigenic properties to dendritic cells by inducing amphiregulin secretion

ATP confers tumorigenic properties to dendritic cells by inducing amphiregulin secretion

Amphiregulin: An early trigger of liver regeneration in mice

Expression and role of EGFR ligands induced in airway cells by PM2.5 and its components

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