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Angiotensin II Regulates the Expression of Monocyte Chemoattractant Protein-1 in Pancreatic Cancer Cells

  • 2009 SSAT Quick Shot Presentation
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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Introduction

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal cancers with an overall median survival of less than 9 months and a 5-year survival rate of less than 5%. Increasing evidence indicates that inflammation facilitates PDA growth.

Discussion

Angiotensin II (AngII), the principal hormone of the renin–angiotensin system, is actively generated in the pancreas and has been proposed as a key mediator of inflammation. Monocyte chemoattractant protein (MCP)-1 is a chemokine that plays an important role in the recruitment of mononuclear cells into sites of inflammation. In this study, we investigated the potential proinflammatory role of AngII in PDA through studying its effect on MCP-1. AngII significantly increased the expression of MCP-1 mRNA and protein in PDA cells and induced its promoter activity. Constitutive and AngII-induced MCP-1 transcription was inhibited by an AngII type 1 receptor (AT1R) blocker, but was unchanged by an AT2R blocker. AngII activated the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, but not p38 or c-Jun NH2-terminal mitogen-activated protein kinases. Inhibition of ERK1/2 activation reduced the AngII-induced MCP-1 synthesis. AngII induced the activation and nuclear translocation of nuclear factor-κB (NF-κB), an effect that was inhibited by AT1R blockade. Inhibition of NF-κB by pyrrolidine dithiocarbamate decreased the AngII-mediated increase in MCP-1 mRNA. Our data provide a novel insight into an AngII-initiated signal transduction pathway that regulates MCP-1 as a possible inflammatory mechanism in PDA and suggest that AngII blockade may regulate chemokine-induced signal transduction to prevent or reduce inflammation in PDA.

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Acknowledgments

This work is supported by a grant from the American Cancer Society (RSG CSM-113191).

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Authors and Affiliations

  1. Department of Surgery, Jefferson Pancreatic, Biliary & Related Cancer Center, Thomas Jefferson University, 1015 Walnut Street, Philadelphia, PA, 19107, USA

    Navdeep Chehl, Qiaoke Gong, Galina Chipitsyna, Tamer Aziz, Charles J. Yeo & Hwyda A. Arafat

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  1. Navdeep Chehl
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  2. Qiaoke Gong
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  3. Galina Chipitsyna
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Correspondence to Hwyda A. Arafat.

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Chehl, N., Gong, Q., Chipitsyna, G. et al. Angiotensin II Regulates the Expression of Monocyte Chemoattractant Protein-1 in Pancreatic Cancer Cells. J Gastrointest Surg 13, 2189–2200 (2009). https://doi.org/10.1007/s11605-009-1055-8

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