Macrophages promote the progression of premalignant mammary lesions to invasive cancer.

Carron, E. C., Homra, S., Rosenberg, J., Coffelt, S. B. , Kittrell, F., Zhang, Y., Creighton, C. J., Fuqua, S. A., Medina, D. and Machado, H. L. (2017) Macrophages promote the progression of premalignant mammary lesions to invasive cancer. Oncotarget, 8(31), pp. 50731-50746. (doi:10.18632/oncotarget.14913) (PMID:28159924)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Coffelt, Dr Seth
Authors: Carron, E. C., Homra, S., Rosenberg, J., Coffelt, S. B., Kittrell, F., Zhang, Y., Creighton, C. J., Fuqua, S. A., Medina, D., and Machado, H. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Oncotarget
Publisher:Impact Journals
ISSN:1949-2553
ISSN (Online):1949-2553
Published Online:31 January 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Oncotarget 8(31): 50731-50746
Publisher Policy:Reproduced under a Creative Commons License

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