Oncotarget

Research Papers:

Macrophages promote the progression of premalignant mammary lesions to invasive cancer

Emily C. Carron, Samuel Homra, Jillian Rosenberg, Seth B. Coffelt, Frances Kittrell, Yiqun Zhang, Chad J. Creighton, Suzanne A. Fuqua, Daniel Medina and Heather L. Machado _

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Oncotarget. 2017; 8:50731-50746. https://doi.org/10.18632/oncotarget.14913

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Abstract

Emily C. Carron1, Samuel Homra1, Jillian Rosenberg1, Seth B. Coffelt2, Frances Kittrell3, Yiqun Zhang4, Chad J. Creighton4, Suzanne A. Fuqua5, Daniel Medina3 and Heather L. Machado1

1Department of Biochemistry and Molecular Biology, Tulane School of Medicine, New Orleans, LA, USA

2CRUK Beatson Institute and Institute of Cancer Sciences, University of Glasgow, Glasgow, UK

3Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

4Dan L. Duncan Comprehensive Cancer Center Division of Biostatistics, Baylor College of Medicine, Houston, TX, USA

5Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA

Correspondence to:

Heather L. Machado, email: hmachado@tulane.edu

Keywords: inflammation, macrophage, early stage lesion, breast cancer progression, mammary

Received: August 15, 2016    Accepted: December 26, 2016    Published: January 31, 2017

ABSTRACT

Breast cancer initiation, progression and metastasis rely on a complex interplay between tumor cells and their surrounding microenvironment. Infiltrating immune cells, including macrophages, promote mammary tumor progression and metastasis; however, less is known about the role of macrophages in early stage lesions. In this study, we utilized a transplantable p53-null model of early progression to characterize the immune cell components of early stage lesions. We show that macrophages are recruited to ductal hyperplasias with a high tumor-forming potential where they are differentiated and polarized toward a tumor-promoting phenotype. These macrophages are a unique subset of macrophages, characterized by pro-inflammatory, anti-inflammatory and immunosuppressive factors. Macrophage ablation studies showed that macrophages are required for both early stage progression and primary tumor formation. These studies suggest that therapeutic targeting of tumor-promoting macrophages may not only be an effective strategy to block tumor progression and metastasis, but may also have critical implications for breast cancer prevention.


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