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Grant Details

Grant Number: 4R01CA160890-05 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: 2016


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.


Spontaneous regression of micro-metastases following primary tumor excision: a critical role for primary tumor secretome.
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Source: BMC biology, 2020-11-06; 18(1), p. 163.
EPub date: 2020-11-06.
PMID: 33158447
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Authors: Alcobia D.C. , Ziegler A.I. , Kondrashov A. , Comeo E. , Mistry S. , Kellam B. , Chang A. , Woolard J. , Hill S.J. , Sloan E.K. .
Source: iScience, 2018-08-31; 6, p. 280-288.
EPub date: 2018-08-11.
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Social regulation of the lymph node transcriptome in rhesus macaques (Macaca mulatta).
Authors: Chun K. , Capitanio J.P. , Lamkin D.M. , Sloan E.K. , Arevalo J.M. , Cole S.W. .
Source: Psychoneuroendocrinology, 2017 02; 76, p. 107-113.
EPub date: 2016-11-14.
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Cancer cells become less deformable and more invasive with activation of β-adrenergic signaling.
Authors: Kim T.H. , Gill N.K. , Nyberg K.D. , Nguyen A.V. , Hohlbauch S.V. , Geisse N.A. , Nowell C.J. , Sloan E.K. , Rowat A.C. .
Source: Journal of cell science, 2016-12-15; 129(24), p. 4563-4575.
EPub date: 2016-11-14.
PMID: 27875276
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β-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.Y. , Arevalo J.M.G. , Cole S.W. , Sloan E.K. .
Source: Brain, behavior, and immunity, 2016 Oct; 57, p. 338-346.
EPub date: 2016-07-30.
PMID: 27485040
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β2-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. .
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Optimized Method for Untargeted Metabolomics Analysis of MDA-MB-231 Breast Cancer Cells.
Authors: Peterson A.L. , Walker A.K. , Sloan E.K. , Creek D.J. .
Source: Metabolites, 2016-09-22; 6(4), .
EPub date: 2016-09-22.
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Long-term Consequences of the Acute Neural-Inflammatory Stress Response in the Cancer Surgical Patient: New Findings and Perspectives.
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Stress-driven lymphatic dissemination: An unanticipated consequence of communication between the sympathetic nervous system and lymphatic vasculature.
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Source: Molecular & cellular oncology, 2016 Jul; 3(4), p. e1177674.
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Neural regulation of cancer: from mechanobiology to inflammation.
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Source: Nature communications, 2016-03-01; 7, p. 10634.
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The β2-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.
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β2-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, 2015-11-25; 17(1), p. 145.
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Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention.
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α2-Adrenergic blockade mimics the enhancing effect of chronic stress on breast cancer progression.
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Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment.
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EPub date: 2013-10-15.
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Bioluminescent orthotopic model of pancreatic cancer progression.
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Source: Journal of visualized experiments : JoVE, 2013-06-28; (76), .
EPub date: 2013-06-28.
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PEGylation of interferon α2 improves lymphatic exposure after subcutaneous and intravenous administration and improves antitumour efficacy against lymphatic breast cancer metastases.
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Source: Journal of controlled release : official journal of the Controlled Release Society, 2013-06-10; 168(2), p. 200-8.
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Chronic stress enhances progression of acute lymphoblastic leukemia via β-adrenergic signaling.
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The sympathetic nervous system induces a metastatic switch in primary breast cancer.
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