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National Institutes of Health: National Cancer Institute: Division of Cancer Control and Population Sciences
Grant Details

Grant Number: 5R01CA160890-02 Interpret this number
Primary Investigator: Sloan, Erica
Organization: University Of California Los Angeles
Project Title: Adrenergic Regulation of Tumor Inflammation and Metastatic Dissemination
Fiscal Year: 2013
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Abstract

DESCRIPTION (provided by applicant): The metastatic microenvironment is receiving increasing attention as a target for new breast cancer therapies. The sympathetic nervous system (SNS) is a component of this microenvironment, and our recent studies indicated that SNS activity may support metastasis through beta-adrenergic pathways that recruit macrophages and induce a switch to pro-metastatic gene expression. Development of novel adjunctive therapeutic strategies that target neural regulation of metastasis requires characterization of the relationships between the SNS, the immune system and tumor cells. To address this need, the proposed studies utilize multimodal in vivo imaging techniques to address the following specific aims: 1. characterize SNS regulation of tumor cells in breast cancer metastasis, 2. characterize SNS regulation of tumor-associated macrophages in breast cancer metastasis, 3. characterize SNS regulation of the tumor microenvironment in breast cancer metastasis. These studies will define interactions between SNS nerve fibers, tumor cells and macrophages in the context of the tumor microenvironment and elucidate their collective effects on metastasis. Given recent clinical studies that suggest beta-blockade reduces breast cancer recurrence, the proposed studies are urgently needed to establish a mechanistic foundation for rapid translation of existing compounds (beta-blockers) and development of novel biomarkers of early cancer progression and new anti-metastatic strategies that target SNS regulation of the tumor microenvironment.

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Publications

The Sympathetic Nervous System Induces A Metastatic Switch In Primary Breast Cancer
Authors: Sloan E.K. , Priceman S.J. , Cox B.F. , Yu S. , Pimentel M.A. , Tangkanangnukul V. , Arevalo J.M. , Morizono K. , Karanikolas B.D. , Wu L. , et al. .
Source: Cancer Research, 2010-09-15 00:00:00.0; 70(18), p. 7042-52.
PMID: 20823155
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Chronic Stress Enhances Progression Of Acute Lymphoblastic Leukemia Via -adrenergic Signaling
Authors: Lamkin D.M. , Sloan E.K. , Patel A.J. , Chiang B.S. , Pimentel M.A. , Ma J.C. , Arevalo J.M. , Morizono K. , Cole S.W. .
Source: Brain, Behavior, And Immunity, 2012 May; 26(4), p. 635-41.
PMID: 22306453
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Pegylation Of Interferon 2 Improves Lymphatic Exposure After Subcutaneous And Intravenous Administration And Improves Antitumour Efficacy Against Lymphatic Breast Cancer Metastases
Authors: Kaminskas L.M. , Ascher D.B. , McLeod V.M. , Herold M.J. , Le C.P. , Sloan E.K. , Porter C.J. .
Source: Journal Of Controlled Release : Official Journal Of The Controlled Release Society, 2013-06-10 00:00:00.0; 168(2), p. 200-8.
PMID: 23499718
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Bioluminescent Orthotopic Model Of Pancreatic Cancer Progression
Authors: Chai M.G. , Kim-Fuchs C. , Angst E. , Sloan E.K. .
Source: Journal Of Visualized Experiments : Jove, 2013; (76), .
PMID: 23852391
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Lymphovascular And Neural Regulation Of Metastasis: Shared Tumour Signalling Pathways And Novel Therapeutic Approaches
Authors: Le C.P. , Karnezis T. , Achen M.G. , Stacker S.A. , Sloan E.K. .
Source: Best Practice & Research. Clinical Anaesthesiology, 2013 Dec; 27(4), p. 409-25.
PMID: 24267548
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Chronic Stress Accelerates Pancreatic Cancer Growth And Invasion: A Critical Role For Beta-adrenergic Signaling In The Pancreatic Microenvironment
Authors: Kim-Fuchs C. , Le C.P. , Pimentel M.A. , Shackleford D. , Ferrari D. , Angst E. , Hollande F. , Sloan E.K. .
Source: Brain, Behavior, And Immunity, 2014 Aug; 40, p. 40-7.
PMID: 24650449
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2-adrenergic Blockade Mimics The Enhancing Effect Of Chronic Stress On Breast Cancer Progression
Authors: Lamkin D.M. , Sung H.Y. , Yang G.S. , David J.M. , Ma J.C. , Cole S.W. , Sloan E.K. .
Source: Psychoneuroendocrinology, 2015 Jan; 51, p. 262-70.
PMID: 25462899
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Neural Regulation Of Pancreatic Cancer: A Novel Target For Intervention
Authors: Chang A. , Kim-Fuchs C. , Le C.P. , Hollande F. , Sloan E.K. .
Source: Cancers, 2015; 7(3), p. 1292-312.
PMID: 26193320
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The 2-adrenoceptor Activates A Positive Camp-calcium Feedforward Loop To Drive Breast Cancer Cell Invasion
Authors: Pon C.K. , Lane J.R. , Sloan E.K. , Halls M.L. .
Source: Faseb Journal : Official Publication Of The Federation Of American Societies For Experimental Biology, 2016 Mar; 30(3), p. 1144-54.
PMID: 26578688
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2-adrenoceptor Signaling Regulates Invadopodia Formation To Enhance Tumor Cell Invasion
Authors: Creed S.J. , Le C.P. , Hassan M. , Pon C.K. , Albold S. , Chan K.T. , Berginski M.E. , Huang Z. , Bear J.E. , Lane J.R. , et al. .
Source: Breast Cancer Research : Bcr, 2015; 17(1), p. 145.
PMID: 26607426
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Chronic Stress In Mice Remodels Lymph Vasculature To Promote Tumour Cell Dissemination
Authors: Le C.P. , Nowell C.J. , Kim-Fuchs C. , Botteri E. , Hiller J.G. , Ismail H. , Pimentel M.A. , Chai M.G. , Karnezis T. , Rotmensz N. , et al. .
Source: Nature Communications, 2016; 7, p. 10634.
PMID: 26925549
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2-adrenoceptors On Tumor Cells Play A Critical Role In Stress-enhanced Metastasis In A Mouse Model Of Breast Cancer
Authors: Chang A. , Le C.P. , Walker A.K. , Creed S.J. , Pon C.K. , Albold S. , Carroll D. , Halls M.L. , Lane J.R. , Riedel B. , et al. .
Source: Brain, Behavior, And Immunity, 2016-06-16 00:00:00.0; , .
PMID: 27321906
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Neural Regulation Of Cancer: From Mechanobiology To Inflammation
Authors: Kim T.H. , Rowat A.C. , Sloan E.K. .
Source: Clinical & Translational Immunology, 2016 May; 5(5), p. e78.
PMID: 27350878
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-adrenergic-stimulated Macrophages: Comprehensive Localization In The M1-m2 Spectrum
Authors: Lamkin D.M. , Ho H.Y. , Ong T.H. , Kawanishi C.K. , Stoffers V.L. , Ahlawat N. , Ma J.C. , Arevalo J.M. , Cole S.W. , Sloan E.K. .
Source: Brain, Behavior, And Immunity, 2016-07-30 00:00:00.0; , .
PMID: 27485040
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